Drugs in blood and urine samples from victims of suspected exposure to drink spiking: A prospective observational study from Oslo, Norway

Vivian M Dalaker; Håvard Furuhaugen; Mette Brekke; Mari Asphjell Bjørnaas; Maja Krpo; Elisabeth Leere Øiestad; Odd Martin Vallersnes

doi:10.1371/journal.pone.0306191

. 2024 Jul 10;19(7):e0306191. doi: 10.1371/journal.pone.0306191

Drugs in blood and urine samples from victims of suspected exposure to drink spiking: A prospective observational study from Oslo, Norway

Vivian M Dalaker ^1,², Håvard Furuhaugen ³, Mette Brekke ⁴, Mari Asphjell Bjørnaas ⁵, Maja Krpo ⁶, Elisabeth Leere Øiestad ^3,⁷, Odd Martin Vallersnes ^1,^2,^*

Editor: Heather M Barkholtz⁸

PMCID: PMC11236145 PMID: 38985694

Abstract

Objective

People regularly contact emergency medicine services concerned that they have been exposed to drink spiking, i.e., exposure to drugs without their knowledge or permission. We identified drugs in blood and urine samples from patients suspecting exposure to drink spiking, with special consideration for drugs not reported taken by the patient (unreported drugs).

Methods

From September 2018 to May 2019, we collected blood and urine samples from patients 16 years or older presenting at an emergency clinic in Oslo, Norway, within 48 hours of suspected exposure to drink spiking. We also collected information on ethanol ingestion and drugs taken. Blood samples were analyzed for 20 classical recreational drugs using ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) and an automated enzymatic method for ethanol. Urine samples were analyzed using immunoassay methods and a specific gas chromatography mass spectrometry (GCMS) method for gammahydroxybutyrate (GHB).

Results

From 100 included patients (median age 24 years, 62 females), we collected 100 blood samples and 72 urine samples. Median time since exposure was 5 hours. Unreported drugs were found in 15 patients. Unreported drugs in the blood samples were clonazepam in 3, methylenedioxymethamphetamine (MDMA) in 3, amphetamine in 2, tetrahydrocannabinol (THC) in 2, tramadol in 1, cocaine in 1, and methamphetamine in 1. Unreported drugs in the urine samples were cocaine in 5, amphetamine in 4, ecstasy in 3, and cannabis in 2. Ethanol was found in 69 patients, all reporting ethanol ingestion. Median blood ethanol concentration was higher in patients with no unreported drugs detected, 1.00‰ (interquartile range (IQR) 0–1.52) vs. 0‰ (IQR 0–0.46) (p<0.001). GHB was not detected.

Conclusion

Unreported drugs, possibly used for drink spiking, were found in 15% of patients. Blood ethanol concentration was higher when no unreported drugs were found. GHB was not detected in any patient.

Introduction

There has been abundant media coverage in several countries during the recent years focusing on drink spiking [1–4]. People presenting with a concern that someone spiked their drink at a party or in a bar or club is a common occurrence in emergency departments [4–7]. Drink spiking is confirmed in some cases, but sometimes appropriate measures are not taken to investigate the claims. Therefore, the extent of the problem is unknown. Previous studies have found that drink spiking with drugs other than ethanol might not be as widespread as the media coverage suggests [4, 6–9].

Most studies on drink spiking have concentrated on drug facilitated sexual assault [8–11]. In systematic reviews of toxicological analyses from victims of drug facilitated sexual assault, the incidence of detection of different substances varies widely: ethanol was found in 10–66% of patients, cannabis in 1–58%, benzodiazepines in 3–83%, cocaine in 1–37%, amphetamines in 1–20%, methylenedioxymethamphetamine (MDMA) in 1–11%, ketamine in 0–18%, and gammahydroxybutyrate (GHB) in 0–6% [8–11]. Several other drugs were also found. In most studies, context information was sparse, and whether substances were taken voluntarily or not was difficult to discern. In a recent review, 2–22% of cases were estimated to result from covert drug administration [8]. In studies of other drug-facilitated crime, analyses have shown different mixtures of benzodiazepines, and also scopolamine, used to incapacitate and then rob the victims [12, 13].

Some people are concerned about exposure to drink spiking though no other crime has happened. There are few studies on such cases, as these patients are not referred to a sexual assault centre or the police for further forensic tests. An Australian study found nine plausible cases among the 97 alleged drink spiking cases they included, five involving ethanol and one GHB [7]. In a study from inner-city London, ethanol was detected in the biological samples in 90% of the 78 participants, and 60% had a blood alcohol concentration above 1.5 g/L [4]. There were eight possible drink spiking cases, where participants tested positive for drugs they denied intentional exposure to; three involving MDMA, three cannabis, one GHB, and one a benzodiazepine [4]. Among 42 patients presenting to an emergency department in Wales alleging their drink had been spiked, none tested positive for GHB or benzodiazepines, while 65% of those tested had a blood alcohol concentration above 1.60 g/L [5].

Many of the drugs potentially used for drink spiking are rapidly eliminated from the body. GHB is often of concern; a colourless, tasteless liquid that easily can be disguised in someone’s drink and is eliminated from the body within 10 hours [14, 15]. Furthermore, varying availability of laboratory testing at emergency departments may lead to delays or to laboratory tests not being taken. Laboratory testing of the suspected spiked drink itself might be a complementary strategy [16]. However, the drink or glass may often not be recoverable.

Objectives

The aim of this study was to identify drugs in blood and urine samples from patients suspecting exposure to spiked drinks. We considered drugs not reported taken by the patient (unreported drugs) as drugs possibly used to spike a drink.

Materials and methods

Design

The study was a prospective observational study. From 1 September 2018 to 31 May 2019, we collected blood and urine samples from patients who presented at the Oslo Accident and Emergency Outpatient Clinic (OAEOC) suspecting exposure to drink spiking.

Setting

The OAEOC is the main primary care emergency outpatient clinic in Oslo, with approximately 200,000 consultations per year, mainly staffed by general practitioners and nurses. The OAEOC serves the entire city (681,071 inhabitants as per 1 January 2019 [17]) at all hours. Short-time observation and an observation unit with 18 beds are available, with limited diagnostic tools and treatment possibilities. In Oslo, the vast majority of patients with recreational drug toxicity are treated at the OAEOC, but the more severe cases are transferred to hospital or brought directly to hospital by the ambulance service [18].

Inclusion

Patients 16 years or older themselves raising concern about possible exposure to drink spiking within the last 48 hours were invited to participate in the study. The concern was either spontaneously raised by the patient at presentation or while consulting a doctor after observation for acute poisoning related to recreational drug use. All patients provided written informed consent before inclusion in the study. Patients who were unconscious or too intoxicated to provide informed consent were invited after having regained their capacity to consent after treatment and/or observation. Treatment was provided according to local procedure [18]. Victims of sexual assault were immediately transferred to the Sexual Assault Centre and not included in the study, as blood and urine sampling for these patients require procedures for maintaining a forensic chain of evidence.

Data collection

Blood and urine samples were obtained by a nurse, and information was collected through a questionnaire administered by the doctor treating the patient.

The patients provided information of intake of alcohol, recreational drugs, and prescription drugs (including prescribed opioids, benzodiazepines, and methylphenidate) during the last 48 hours (asked as an open question, no predefined categories), and details of the symptoms and clinical features that led to concern about exposure to drink spiking (amnesia, different drug effect experience than expected, more/less hangover, or other causes). Details concerning the time, place, and observations by relatives or friends were recorded. We also registered age, gender, time (or time period) for ingestion of a possibly spiked drink, symptoms at presentation, clinical features at presentation (level of consciousness (Glascow Coma Scale score), heart rate, blood pressure, temperature, and respiratory rate), and treatment. We also registered the results of any supplementary investigations, e.g., electrocardiogram or other blood samples.

Toxicological sampling and analyses

Venous blood samples were collected in serum tubes (BD Vacutainer) and stored in a refrigerator at 4°C before being transported in a cooler bag approximately once a week to the Section of Drug Abuse Research, Department of Forensic Sciences, Oslo University Hospital, for analysis. In a few cases where transport was not possible within one week, the blood samples were temporarily frozen. Whole blood concentrations were determined using ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) for amphetamine, methamphetamine, MDMA, cocaine, benzoylecgonine, tetrahydrocannabinol (THC), alprazolam, diazepam, flunitrazepam, clonazepam, nitrazepam, oxazepam, zolpidem, zopiclone, buprenorphine, codeine, methadone, morphine, and tramadol [19]. In brief, samples were prepared using supported liquid extraction with ethylacetate:heptane (80:20 v:v) and analysed using a Waters Aquity UPLC® HSST3 column, 2.1 x 100 mm, 1.8 μm particles (Waters, MA, USA) using methanol and 10 mM ammonium formate buffer pH 3.1 as mobile phase. Mass detection was performed in positive electrospray mode on a Waters TQS instrument (Waters, MA, USA). Ethanol (alcohol) was analysed on an AU680 clinical chemistry analyzer (Beckman Coulter, Brea, CA, USA) by an automated enzymatic method using alcohol dehydrogenase [20]. A modification of a previously published method [21] was used for GHB in blood, only the sample preparation was done using Captiva Lipid ND 96-well plates in stead of OASIS HLB 96-well extraction plates. A similar instrumental set up to the general drug determination using a T3 column and a Xevo TQS instrument was applied, however 0.2% formic acid and methanol were used as mobile phase constituents. Reporting limits in the blood samples are shown in S1 Table in S1 File.

The urine samples (collected in Urin-Monovette with no additives) were stored in a refrigerator at 4°C before being sent on to the The Department of Pharmacology, Oslo University Hospital Ullevaal for screening analysis every 24 hours. An immunoassay screening method based on spectrophotometry was used and performed on the AU680 clinical chemistry analyzer (Beckman Coulter, Brea, CA, USA). Urine samples were screened for amphetamines (EMIT d.a.u. reagents from Siemens, SYVA), benzodiazepines, opiates, cocaine, THC and metabolites (CEDIA TDM reagents from Thermo Fisher Scientific), ethanol, and ecstasy (MDMA, methylenedioxyamphetamine (MDA), methylenedioxyethylamphetamine (MDEA), methylbenzodioxolylbutanamine (MBDB), benzodioxolylbutanamine (BDB), paramethoxyamphetamine (PMA), and paramethoxymethamphetamine (PMMA)) (DRI TDM reagents from Thermo Fisher Scientific, Waltham, MA, USA). Measurements of pH and creatinine were performed. GHB was tested for in all urine samples, using a specific gas chromatography mass spectrometry (GC-MS) method. GHB analysis was performed by headspace GC coupled to a mass spectrometer. The system consisted of a 7697 Headspace Sampler, a 7890B GC system and a 5977A MSD mass spectrometer, all from Agilent Technologies (Santa Clara, CA, USA). GHB was converted to gammabutyrolactone (GBL) by using sulphuric acid as a catalyst in a headspace vial. The MS is operated in EI mode (70 eV), and GBL was determined using m/z 86 (quantifier ion) and m/z 56 (qualifier ion). α-methyl GBL (AMGBL) was used as an internal standard. The headspace and GC settings were: transfer line at 280°C, loop at 250°C, oven temperature 170°C isothermal, carrier gas helium at flow 1 ml/min, column DB-624 UI. Cut-off values for the urine samples are shown in S2 Table in S1 File.

Information about the toxicological results was provided to patients by the study investigator (VMD) by telephone. At the same time the previously collected information was confirmed or corrected.

Outcome measures

Unreported drugs were defined as drugs found in blood and/or urine not reported taken by the patient within the previous 48 hours. We considered the unreported drugs as drugs possibly used to spike a drink.

Ethics

The study was performed in accordance with the Helsinki declaration. Participants provided written informed consent. The study was approved by the Oslo University Hospital Information Security and Privacy Office and by the Regional Committee South-East for Medical and Health Research Ethics (REK sør-øst D 2017/1880).

Study registration

The study was registered at ClinicalTrials.gov (NCT03651778).

Statistics

Analyses were done in IBM SPSS versions 28–29 (IBM Corp, Chicago, IL). Pearson’s chi-square test or Fisher’s exact test (for expected cell counts of five or less) were used to compare frequencies. Mann–Whitney U-test was used in comparisons of continuous variables. Missing data were not included in the analyses.

Results

During 37 weeks, 100 patients (2.7 per week) were included. Median age was 24 years (range 16–63), 62 were females, 38 were males. We collected 100 blood samples and 72 urine samples. Unreported drugs were found in 15 patients.

Reasons reported for suspecting exposure to drink spiking were the same whether unreported drugs were found or not (Table 1). Median time from ingestion of a suspected spiked drink to biological sampling was 12 hours when unreported drugs were found, and 4 hours when not (p = 0.02). We obtained blood samples from 48 of the patients within 4 hours (urine from 35), from 74 patients within 12 hours (urine from 56), and from 95 patients within 24 hours (urine from 70). The most commonly reported symptoms were amnesia (63%), vomiting (20%), nausea (14%), feeling intoxicated/drunk (13%), and dizziness (12%).

Table 1. Reasons for suspecting exposure to drink spiking, symptoms at presentation, and clinical observations.

	Cases with any drug not reported taken by the patient	Cases with only drugs reported taken by the patient	Total
	n (%) / median (IQR)	n (%) / median (IQR)	n / median (IQR)
Sex
Females	8 (53)	54 (64)	62
Males	7 (47)	31 (37)	38
Age (years)	27 (22–32)	23 (20–30)	24 (20–31)
Reasons for suspecting exposure to drink spiking
Different drug effect experience	11 (73)	57 (67)	68
Amnesia	7 (47)	56 (66)	63
More/less hangover	6 (40)	18 (21)	24
Other reason	9 (60)	42 (49)	51
Symptoms reported
Vomiting	3 (20)	17 (20)	20
Nausea	3 (20)	11 (13)	14
Feeling drunk/intoxicated	3 (20)	10 (12)	13
Dizziness	4 (27)	8 (9)	12
Clinical observations at presentation
Glasgow Coma Scale score	15 (15–15)^a	15 (15–15)^b	15 (15–15)^b
Respiratory rate (per minute)	15 (14–17)	16 (14–17)	16 (14–17)
Heartrate (beats per minute)	96 (77–106)	86 (76–98)	87 (76–97)
Systolic blood pressure (mmHg)	131 (118–137)	121 (114–131)	122 (114–131)
Temperature (°C)	36.5 (36.2–36.9)	36.3 (35.7–36.7)	36.3 (35.7–36.7)
Time since suspected exposure (hours)	12 (4–24)	4 (2–12)	5 (2–14)
Serum ethanol concentration (‰)	0 (0–0.46)	1.00 (0–1.52)	0.89 (0–1.42)
Number of drugs other than ethanol
1	8 (53)	5 (6)	13
2	5 (33)	-	5
≥3	2 (13)	-	2
Total	15 (100)	85 (100)	100

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IQR: interquartile range.

No statistically significant differences between groups, except for time since suspected exposure p = 0.033, serum ethanol p<0.001, and number of drugs found p<0.001.

^aAll patients had Glasgow Coma Scale score 15.

^bGlasgow Coma Scale score range 12–15.

Among the 91 patients reporting having ingested ethanol, it was detected in blood in 66 (among them also in urine in 46), and in urine only in another three. Median blood ethanol concentration was higher when no unreported drugs were found, 1.00‰ (interquartile range (IQR) 0–1.52) vs. 0‰ (IQR 0–0.46) (p<0.001) (Table 1). In general, blood ethanol concentration was lower the longer time since the incident (Fig 1). Median blood ethanol concentration, when detected, was 1.25‰ (IQR 0.90–1.61; range 0.03–3.47). Ethanol was not detected in either matrix in any of the nine patients not reporting ingestion, amongst whom six presented within three hours of the incident.

The unreported drugs found in the blood samples were clonazepam in 3 (3%), MDMA in 3 (3%), amphetamine in 2 (2%), THC in 2 (2%), tramadol in 1 (1%), cocaine in 1 (1%), and methamphetamine in 1 (1%) (Tables 2 & 3). The unreported drugs found in the urine samples were cocaine in 5 (7%), amphetamine in 4 (6%), ecstasy in 3 (4%), and cannabis in 2 (3%). Not counting ethanol, more than one drug was found in 7 cases, all of them among the cases with unreported drugs. There were some discrepancies between findings in blood and urine (Table 3). GHB was not detected in either blood or urine samples.

Table 2. Substances found in blood and urine samples in patients suspecting exposure to drink spiking.

	Samples with any substance not reported taken by the patient	Samples without substances not reported taken by the patient	Total samples with substance
	n (%)	n (%)	n (%)
Blood
Any substance	12 (100)^a	69 (78)^a	75 (75)^a
Clonazepam	3 (25)	-	3 (3)
MDMA	3 (25)	-	3 (3)
Amphetamine	2 (17)	1 (1)	3 (3)
THC	2 (17)	1 (1)	3 (3)
Cocaine	1 (8)	1 (1)	2 (2)
Tramadol	1 (8)	-	1 (1)
Methamphetamine	1 (8)	-	1 (1)
Ethanol	-	66 (75)	66 (66)
Alprazolam	-	1 (1)	1 (1)
Total blood samples	12 (100)	88 (100)	100 (100)
Urine
Any substance	10 (100)^a	53 (85)^a^a	56 (78)^a
Cocaine	5 (50)	2 (3)	7 (10)
Amphetamine	4 (40)	1 (2)	5 (7)
Ecstasy ^b	3 (30)	-	3 (4)
Cannabis	2 (20)	4 (6)^c	6 (8)
Ethanol	-	49 (79)	49 (68)
Benzodiazepines	-	1 (2)	1 (1)
Opiates	-	1 (2)	1 (1)
Total urine samples	10 (100)	62 (100)	72 (100)

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^aAny substance total is less than the sum of individual substances, as several drugs were detected in several cases, cf. Table 3.

^bMDMA and related drugs.

^cIn all 4 cases, cannabis not reported used last 48 hours; found in urine, not in blood. Probably metabolites from previous cannabis use.

MDMA: methylenedioxymethamphetamine; THC: tetrahydrocannabinol.

Table 3. Patients suspecting exposure to drink spiking, with drugs other than ethanol detected in blood and/or urine sample (n = 19).

Gender/age	Substance	Blood concentration nM	Detected in urine	Time since suspected exposure (hours)	Drug not reported taken	Symptoms and clinical features
M26 ^a	Clonazepam	282		2	X	Dizzy, tired, fainting, amnesia, different drug effect experience than expected
	Amphetamine	3131	Yes		X
	Alprazolam	139
	Benzodiazepines		Yes
	Opiates		Yes
	Cannabis		Yes
F21 ^a	Clonazepam	20		1	X	Paranoid, apparently intoxicated
	Amphetamine	1692	Yes
	Cannabis		Yes
M17 ^b	Clonazepam	99		1	X	Body pain
F29 ^b	Tramadol	211	No urine sample	24	X	Different drug effect experience than expected, more hangover, felt unwell, tired, stomach pain, diarrhoea, nausea, vomiting, fever, disoriented, fainted
F21	MDMA	4312	Yes	12	X	Different drug effect experience than expected, unwell, nauseous
	Amphetamine		Yes		X
F29	MDMA	968	Yes	19	X	Drank water, immediately unwell, vomiting, disoriented, paranoid, mydriasis, then miosis, iris colour changed
	Amphetamine		Yes		X
F51 ^b	MDMA	211	No urine sample	24	X	Different drug effect experience than expected, more hangover, dizzy, cold, difficult to move
M32 ^b	Methamphetamine	790	No urine sample	19	X	Amnesia, different drug effect experience than expected, paranoid, stressed, overactivated, restless, afraid to die, suicidal thoughts
	Cannabis	3	No urine sample
F28	Amphetamine	436	Yes	8	X	Hectic, agitated, thirsty, stressed, restless, mydriasis, thirsty, jaw pain
	Cocaine		Yes		X
	Ethanol	1.47	Yes
M37	Cocaine	53	Yes	10	X	Amnesia, different drug effect experience than expected, felt intoxicated, visual disturbances
	Benzoylecgonine	1529			X
	Ethanol		Yes
M25	Cocaine		Yes	8	X	Amnesia, different drug effect experience than expected, more hangover, felt unwell, unfocused
	Ethanol	0.46	Yes
F22 ^b	Cocaine		Yes	37	X	Amnesia, more hangover, vomiting, chest pain, breathlessness
M27 ^b	Cocaine		Yes	36	X	Amnesia, different drug effect experience than expected, felt warm, blackout, strange behaviour, tired, felt distant and unwell
	MDMA		Yes		X
F35	Cannabis	3	Yes	14	X	Amnesia, different drug effect experience than expected, more hangover, palpitations, felt dizzy and strange
	Ethanol	0.55	Yes
M24	Cannabis	3	Yes	4	X	Trembling, felt unwell, nauseous
	Ethanol	1.24	Yes			Trembling, felt unwell, nauseous
M29	Cocaine	94	Yes	1		Arms felt paralyzed
	Benzoylecgonine	238
	Cocaethylene	63
	Ethanol	1.63	Yes
F30 ^b	Cocaine		Yes	14		Different drug experience than expected, felt powerless, not able to move, headache, tired
M33 ^a	Cannabis		Yes	10		Different drug effect experience than expected, more hangover, felt distant, diplopia, behaved differently
	Ethanol	1.14	Yes
F20 ^a ^, ^b	Cannabis		Yes	19		Amnesia

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^aCannabis not reported used last 48 hours; found in urine, not in blood. Probably metabolites from previous cannabis use.

^bEthanol reported ingested, but not found in blood or urine.

Cannabis: tetrahydrocannabinol in blood; tetrahydrocannabinol and metabolites in urine.

MDMA: methylenedioxymethamphetamine in blood; methylenedioxymethamphetamine and related substances in urine (methylenedioxyamphetamine (MDA), methylenedioxyethylamphetamine (MDEA), methylbenzodioxolylbutanamine (MBDB), benzodioxolylbutanamine (BDB), paramethoxyamphetamine (PMA), and paramethoxymethamphetamine (PMMA)).

Sixty-four (64%) patients were discharged without any observation or treatment, 30 (30%) were kept for observation for some hours (median 3 hours, range 1–4), 10 (10%) were given symptomatic treatment, none were given antidote, and 6 (6%) were transferred to hospital due to need for further treatment of poisoning. No patients died.

Discussion

Unreported drugs were found in 15 of the 100 patients and included clonazepam, tramadol, MDMA, cocaine, amphetamine, methamphetamine, and THC. GHB was not detected. Ethanol was detected in blood in 66 of the 91 patients reporting ingestion, and in urine only in another three. Blood ethanol concentration was higher when no unreported drugs were found.

Possible drink spiking cases

We found unreported drugs in only 15% of the patients suspecting exposure to drink spiking. This is in accordance with the estimate of 2–22% in a recent review [8]. However, cases of drink spiking may have gone undetected, as drugs we did not screen for may be used to spike drinks. We did not analyze for antihistamines, antidepressants, or ketamine, drugs not uncommonly detected in victims of drug facilitated sexual assault [8, 10]. Nor did we analyze for any of the numerous novel psychoactive substances that have appeared during the last two decades, also having a potential to be used for drink spiking [22–25]. Furthermore, a drug taken by the patient may also have been used for drink spiking, adding to the effect of the drug voluntarily taken. Hence, our study probably underestimates the proportion actually subjected to drink spiking among those raising concern.

Clonazepam was detected in three cases, the only benzodiazepine found among the unreported drugs in our study. This is surprisingly few considering how frequently benzodiazepines are detected in drug-facilitated sexual assault [8], though in line with the few reports from other emergency department settings [4, 5, 7]. Benzodiazepines are CNS depressants controlled under drug or medicine legislation and can induce confusion, impaired thinking, memory loss, drowsiness, sleepiness, fatigue, impaired coordination, and dizziness [26]. Flunitrazepam (marketed under the name Rohypnol) has previously been associated with drink spiking, prompting the manufacturer (Roche Pharmaceuticals, Basel, Switzerland) to modify the product formulation and add a colourant, a blue dye fizzing in liquids [10]. Flunitrazepam has been deregistered in Norway but is still used illegally [27]. Clonazepam and diazepam currently dominate in recreational drug toxicity and driving under the influence of drugs cases in Norway [27, 28].

Surprisingly, GHB was not detected in any of the samples, although it is often suspected in drink spiking cases, both by patients and by doctors [5, 10]. The window of detection is relatively short; GHB is eliminated from plasma with a half-life of 30–50 minutes and is detectable in urine for 3 to 10 hours [15]. More than half of our patients had samples taken within the window of detection, as we obtained blood samples from 48 of the patients within 4 hours, and urine samples from 56 patients within 12 hours. In a similar study in London, GHB was detected in blood and urine in only one of 78 participants, who had ingested what he thought was an alcoholic drink at a club [4]. Likewise, GHB used for drink spiking was only found in one of 101 patients in a similar Australian study [7].

MDMA was detected in four drink spiking cases, mostly combined with other drugs and/or ethanol. In recent years the popularity of this drug has increased in Europe [29]. MDMA is an empathogen with some stimulant effects, in itself not associated with sedation, but might lead to disinhibition, and for that reason it is conceivable that this drug can be used to spike someone’s drink [4, 30]. We also found cocaine, amphetamine, and methamphetamine in some drink spiking cases, often combined with each other, alcohol and/or MDMA, similar to findings from the UK [4, 5]. Stimulants do not lead to memory loss, but as other recreational drug they have disinhibiting effects that lead to impaired control, which is a risk factor for drug facilitated sexual assault [30].

Unreported cannabis was detected in urine in six cases, in two of them also in blood, all samples obtained within 19 hours of exposure. In two cases, cannabis only found in urine was the only unreported drug. THC is usually not detectable in blood 24 hours after intake, but metabolites can be detected in urine for weeks after use [31]. It is highly likely that the cannabis only detected in urine samples stemmed from cannabis use more than 48 hours before presentation and hence not reported, rather than covert cannabis administration. Accordingly, we did not consider cannabis only detected in urine an unreported drug.

Ethanol

Nearly all patients reported ingesting ethanol. One out of four patients presented 14 hours or later after the suspected time of exposure to drink spiking, which is probably why ethanol in many cases was not detected (Fig 1). Ethanol has a sedative effect that causes loss of self-control and impaired consciousness, and the effect is enhanced when combined with drugs. The possibility that ethanol, rather than another drug, is used to spike an alcoholic drink to amplify the sedative effect, is also a plausible explanation for intoxication that does not correspond to what people thought they had been drinking. Our finding that blood ethanol concentrations were higher when no unreported drugs were detected might result from drink spiking with ethanol. On the other hand, these patients presented earlier, which also may explain the higher blood ethanol concentrations. It is also possible that people may underestimate the amount or the effect of the alcohol they have ingested. In a study among 264 patients at a Norwegian sexual assault centre, covert drug administration was more often suspected by the patient the higher the blood ethanol concentration [32]. In our study one out of four had 1.42‰ or above, in line with other studies, emphasizing high ethanol concentrations as a possible explanation for the patient’s condition [4, 5, 8, 32]. Whether the ethanol was voluntarily ingested or covertly administered remains hard to prove.

Testing for drink spiking

Suspected exposure to drink spiking is a major concern for the victim, also in the absence of any additional crime. Most people would like to know whether an exposure actually happened. However, there are significant barriers to having this service available, including timing, cost, and providing analysis that covers for the many hundred possible drugs. Limited analytical libraries may give false negative results. Keeping up with the expanding abundance and variety of the novel psychoactive substances is a challenge to clinicians, developers of toxicological tests, and legislatures [25, 33, 34]. More importantly, it constitutes an additional health hazard as users are often not aware of the potential dangers of the novel drug at hand [25]. The situation calls for comprehensive international efforts in toxicovigilance, information exchange, and regulative measures [25, 33].

Another issue is the appropriateness of using emergency departments for this service as most patients were clinically well when they presented. Furthermore, in many jurisdictions, emergency department analyses may not be admissible in a court of law. Still, the service is clearly important to the public [1–3].

Strengths and limitations

Our study is one of very few exploring suspected drink spiking cases in the absence of any additional crime.

There may be some uncertainty in the information regarding the reported intake of ethanol and/or drugs and time of suspected exposure to drink spiking, due to intoxication, amnesia or confusion, but most of the patients have confirmed or corrected their information through a telephone consultation conducted when the test results were available. At this time, patients could also confirm or correct which drugs they had taken, both recreational drugs and prescription drugs. However, we must take into account that some might not want to inform about the use of drugs or did not know that drugs taken days or weeks ago still could be detected, such as cannabis in urine.

As far as we know, all patients raising concern about exposure to drink spiking were offered participation in the study. At the time, laboratory toxicological testing was not part of standard care for patients not reporting sexual assault. Consequently, it is highly likely that nearly all eligible patients were included. After the study period, toxicological testing in urine samples was made standard care.

Some cases may have been missed because the patient was brought directly to the hospital by ambulance for treatment due to severe toxicity, bypassing the OAEOC. Pointing in the same direction, most of our patients had a Glasgow Coma Scale score of 15 at presentation. Hence, our population of relatively not severely sick patients may not be representative for the larger population of patients with suspected drink spiking.

The analysis of both blood and urines samples were done using validated methods. However, we did not follow procedures for maintaining a forensic chain of evidence. This may partially explain some of the missing urine samples. We obtained blood samples from all of the 100 patients included, but urine samples from only 72. Some of the patients were not able to provide a urine sample, and some samples were handled inappropriately, and in a few cases lost during transport.

The blood samples were transported once a week to the laboratory. Hence, more than three days might elapse between sampling and analysis, yielding reduced GHB levels [35]. However, it is unlikely that the storage time should reduce the GHB levels below the level of detection. The lack of detection of GHB in the urine samples, transported to the laboratory and analyzed at a daily basis, further supports the validity of this result.

Conclusions

We found a variety of drugs reported taken by the patient. Unreported drugs were found in one of six cases, probably representing drink spiking with benzodiazepines, tramadol, MDMA, amphetamines, cocaine, and cannabis. We found no GHB. Ethanol was widely reported, and blood alcohol concentrations were high among some. Whether ethanol was used to spike alcoholic drinks in our patients is impossible to assess, but clinicians should be observant to the possibility.

Drink spiking is of serious concern to individuals thinking themselves possibly exposed. Laboratory testing can help to some extent, though limited analytical libraries and timing issues are a problem. Furthermore, drinks may be spiked with ethanol, or with a drug also taken voluntarily by the patient. Then, there is the possibility that the patient underestimates the effects of ethanol and/or drugs taken intentionally. All these factors should be considered when addressing the concern of the patient suspecting exposure to drink spiking.

Supporting information

S1 Checklist. STROBE statement—Checklist of items that should be included in reports of cross-sectional studies.

(DOC)

pone.0306191.s001.doc^{(81KB, doc)}

S1 File. S1 and S2 Tables.

Reporting limits in blood samples and cut-off values in urine samples.

(PDF)

pone.0306191.s002.pdf^{(99.9KB, pdf)}

Acknowledgments

Our colleagues at the OAEOC are gratefully acknowledged for including the patients in the study and collecting the blood and urine samples.

This work was performed on the Services for sensitive data (TSD) facilities, owned by the University of Oslo, operated and developed by the TSD service group at the University of Oslo, IT-Department (USIT), (tsd-drift@usit.uio.no).

Data Availability

Data cannot be shared publicly because public deposition would breach compliance with the protocol approved by our research ethics board, the Regional Committee South-East D for Medical and Health Research Ethics. Inquiries about the data and conditions for access can be made to the corresponding author or to the Institute of Health and Society at the University of Oslo, info@helsam.uio.no.

Funding Statement

This work was supported by the Norwegian Research Fund for General Practice. The funder played no role in the research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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PLoS One. doi: 10.1371/journal.pone.0306191.r001

Decision Letter 0

Miquel Vall-llosera Camps

9 Jan 2024

PONE-D-23-26541Drugs in blood and urine samples from suspected spiked drink victims: a prospective observational study from Oslo, NorwayPLOS ONE

Dear Dr. Vallersnes,

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Reviewer #1: Yes

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Reviewer #4: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

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Reviewer #3: Yes

Reviewer #4: N/A

**********

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Reviewer #1: Yes

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Reviewer #4: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Dear Authors,

It was my pleasure to review the article titled Drugs in blood and urine samples from suspected spiked drink victims: a prospective

observational study from Oslo, Norway, a solid and well researched article centered around drug-facilitated sexual assault (or less commonly other crimes targeting an uncconscious ibìncapacitated victim). The study encompasses a 100-patient sample and focuses on detection of unreported drugs.

The article has noteworthy strengths: it is thorough in terms of pursuing its stated objective; it is relevant and overall a worthy contribution to toxicology research; it has an element of novelty in its design, and relies on sound methodology as far as I was able to determine.

It is my belief that the article, particularly in its discussion, could benefit from a slightly higher degree of contextualization and broader scope when it comes to screening and detection techniques. It would certainly make the article more comprehensive and well-rounded to draw comparisons and outline distinctive features of various techniques and their analytical value in terms of tackling the spread of illegal/misused substances, both for recreational use and as a tool to victimize others. Broader remarks on the legal and law enforcement potential of detection efforts, at least within the European context, could also be advisable. The following sources should be drawn upon and cited:

Brunetti P, Lo Faro AF, Di Trana A, Montana A, Basile G, Carlier J, Busardò FP. β'-Phenylfentanyl Metabolism in Primary Human Hepatocyte Incubations: Identification of Potential Biomarkers of Exposure in Clinical and Forensic Toxicology. J Anal Toxicol. 2023 Jan 24;46(9):e207-e217. doi: 10.1093/jat/bkac065.

Di Trana A, Brunetti P, Giorgetti R, Marinelli E, Zaami S, Busardò FP, Carlier J. In silico prediction, LC-HRMS/MS analysis, and targeted/untargeted data-mining workflow for the profiling of phenylfentanyl in vitro metabolites. Talanta. 2021 Dec 1;235:122740. doi: 10.1016/j.talanta.2021.122740.

Lo Faro AF, Venanzi B, Pilli G, Ripani U, Basile G, Pichini S, Busardò FP. Ultra-high-performance liquid chromatography-tandem mass spectrometry assay for quantifying THC, CBD and their metabolites in hair. Application to patients treated with medical cannabis. J Pharm Biomed Anal. 2022 Aug 5;217:114841. doi: 10.1016/j.jpba.2022.114841.

Busardò FP, Zaami S, Baglio G, Indorato F, Montana A, Giarratana N, Kyriakou C, Marinelli E, Romano G. Assessment of the stability of exogenous gamma hydroxybutyric acid (GHB) in stored blood and urine specimens. Eur Rev Med Pharmacol Sci. 2015 Nov;19(21):4187-94.

The tables and figures are qite well crafted and effective at conveying key points and relevant findings.

Although the article is well-written overall, I recommend further proofreading by a native speaker of English.

Reviewer #2: The article is competently assembled and straightforward enough overall. Its aim is clearly delineated and the methodology appears to be sound. tables and figures contribute to the conveyance of key elements providing substance and clarity to the article' s fundamental reasoning and conclusions.

The Discussion I believe should be further developed to better highlight the article's relevance in toxicology research. More meaningful sources ought to be used in order to better elaborate on detection techniques and their value in tackling substance abuse and in upholding public health. The following should be looked at and cited in that regard: DOI: 10.23750/abm.v92i6.12696; DOI 10.1016/j.jpba.2020.113335. Furthermore, I suggest the authors brefly address legislative aspects as well against the backdrop of the major threat posed by novel psychoactive substances DOI: 10.1002/hup.2727; DOI: 10.1007/164_2018_160; DOI: 10.26355/eurrev_201911_19529). Such additions will provide an extra degree of elaboration which will highlight the importance and value of the article's conclusions and findings.

Sincerely.

Reviewer #3: Comments:

1. In abstract (line no 47), Check the sentence consistency.

2. Remove drink spiking word from the keyword.

3. Literature survey regarding analysis of drugs in case of drug facilitated crimes (DFC) is insufficient. The author needs to discuss the recently published analytical methods. The following papers may be cited and discussed in literature survey:

• Exploiting the potential of fabric phase sorptive extraction for forensic food safety: analysis of food samples in cases of drug facilitated crimes. Food chemistry, 432, 137191.

• Cellulose Paper Sorptive Extraction (CPSE) Combined with Gas Chromatography–Mass Spectrometry (GC–MS) for Facile Determination of Lorazepam Residues in Food Samples Involved in Drug Facilitated Crimes. Separations, 10(5), 281.

4. Line no 186; the author should mention the temperature at which the urine and blood samples were stored.

5. The author mustprovide the instrumental specifications of UHPLC-MS/MS and GC-MS used in determining drugs in blood and urine samples within the main manuscript.

6. What is “IQR”? The author must furnish information regarding this term for better understanding of readers.

7. The author must include the chromatograms in the main manuscript for the better understanding of the readers.

Reviewer #4: The manuscript entitled “Drugs in blood and urine samples from suspected spiked drink victims: a prospective observational study from Oslo, Norway” describes an important subject.

However, the manuscript should be corrected to be written in more standard English. There are many typos and unclear definitions (unreported drugs, spiked drinks, voluntary taken etc.), and the manuscript is generally unfocused on the aim and clear conclusions are lacking. It is unclear whether the purpose is to identify which substances are used in these cases or whether the purpose is to make a comparison of identified substances in blood and urine. The authors are encouraged to include more relevant drug classes such as sedative antihistamines, antidepressants etc. to increase the value of the study.

Words/terms which advantageously could be rephrased/changed in the manuscript:

• The authors use the term “patients” throughout the manuscript. I see the point using the term “patients” when the individuals are hospitalized or involved with the emergency medicine services. However, in some sentences it would be more correct to use individuals or victims of drink spiking. As being the case in the objective “patients regularly contact”

• Rephrase the objectives where the sentence say “patients with suspected spiked drinks”. Maybe write suspected victims of drink spiking instead.

• The authors should be consistent with the term drink spiking/spiked drink/drink-spiking throughout the manuscript. They could consider to use drink spiking and victims of dink spiking throughout the manuscript instead of spiked drink victims. Also consider to correct the title.

• Consider to rephrase “unreported drugs” as this in many sentences is confusing. Consider to use “additional drugs which was not self-reported”

• Consider to change the key-words as some are also included in the title. Use only drink spiking or spiked drinks (Depending on which definition is used throughout the manuscript). Consider to include LC-MS/MS in keywords. The keywords deviates from manuscript to the front template.

Selected comments

Abstract:

• In objectives please, clarify the aim of the study.

• The conclusion in the abstract should be changed as this does not really include all important conclusion from the paper. Could the additional drugs measured, which have not been self-reported, potentially contribute to the drink spiking cases?

Introduction:

• The introduction should be shortened and focusing more on the aim of the study.

Materials and methods:

• It is unclear whether the substances are only screened or whether they are also verified.

• Include a more detailed description on the analytical methods used.

Result:

• Line 234 rephrase: we obtained biological samples in blood.

• Table 2: Misleading numbers in the table: is total number of cases in the reported and unreported 100 in each? while the total number is also 100.

• Table 3: Why mention the symptoms and clinical features if they are not used in the classification of "drink spiking".

Discussion:

• The authors write on page 20 line 413 that antidepressants and antihistamines and other drugs not uncommonly found in DFSA cases have not been included in the study. According to SOFT and the drug-facilitated crimes (DFC) committee both antihistamines and antidepressants are among the common DFC drugs in urine samples. Maybe there would be more than 15% of the cases with additional drugs than the self-reported if these compounds have been included. Please elaborate more on that in the manuscript.

• What can this study be used for? What do the reader achieve by reading the paper?

• The study indicates that ethanol could potential be used in drink spiking, and this conclusion is based upon no additional drug findings in the samples and more alcohol in the samples with no additional drug findings. However, this cannot be proven with methods and therefore not give any answers to the victims. What about the samples with other drug findings, could they potentially contribute to the drink spiking cases? More about the actual findings are missing. And could drugs that are commonly taken (antihistamines and antidepressants?) not be used in drink spiking cases? Please elaborate on this also.

• Part conclusions contain too many non-scientific claims such as "The patient may have smokey what they thought was nicotine" line 351 and "Ethanol might have been used to spike alcoholic drinks" line 425 and section 358–371.

• Elaborate more on the ethanol results according to sampling time interval. Many of the samples were collected late, which could be the reason for lack of ethanol detection.

Conclusion:

• What about the actual drug findings, these are not really elaborated?

• Elaborate on the aim.

**********

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

Reviewer #4: No

**********

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PLoS One. 2024 Jul 10;19(7):e0306191. doi: 10.1371/journal.pone.0306191.r002

Author response to Decision Letter 0

7 Mar 2024

Dear editors and reviewers

Thank you for your valuable comments and this opportunity to revise and improve our manuscript.

REVIEWER 1

It was my pleasure to review the article titled Drugs in blood and urine samples from suspected spiked drink victims: a prospective observational study from Oslo, Norway, a solid and well researched article centered around drug-facilitated sexual assault (or less commonly other crimes targeting an uncconscious ibìncapacitated victim). The study encompasses a 100-patient sample and focuses on detection of unreported drugs.

We have elaborated on these points in the Discussion, drawing upon some of the suggested sources (lines 398-403 and 442-446, cf. also response to Reviewer 2).

The tables and figures are qite well crafted and effective at conveying key points and relevant findings.

Although the article is well-written overall, I recommend further proofreading by a native speaker of English.

We have proofread the manuscript again for English language improvement and made appropriate changes throughout.

REVIEWER 2

The article is competently assembled and straightforward enough overall. Its aim is clearly delineated and the methodology appears to be sound. tables and figures contribute to the conveyance of key elements providing substance and clarity to the article' s fundamental reasoning and conclusions.

We have elaborated on these points in the Discussion, drawing upon some of the suggested sources (lines 398-403, cf. also response to Reviewer 1, and lines 411-412), and substantiated what was previously the last paragraph in the Strengths and limitations section (now moved to the Possible drink spiking cases section) with more and appropriate sources (lines 326-332).

Furthermore, I suggest the authors brefly address legislative aspects as well against the backdrop of the major threat posed by novel psychoactive substances DOI: 10.1002/hup.2727; DOI: 10.1007/164_2018_160; DOI: 10.26355/eurrev_201911_19529). Such additions will provide an extra degree of elaboration which will highlight the importance and value of the article's conclusions and findings.

We have addressed the issue of novel psychoactive substances more thoroughly in our revised Discussion (lines 398-403). We have also substantiated our discussion of novel psychoactive substances with the suggested sources (lines 398-403 and 327-332).

REVIEWER #3:

1. In abstract (line no 47), Check the sentence consistency.

We have corrected the sentence.

2. Remove drink spiking word from the keyword.

We have kept drink spiking, but removed spiked drinks from the key words, cf. comment from reviewer 4, below.

• Exploiting the potential of fabric phase sorptive extraction for forensic food safety: analysis of food samples in cases of drug facilitated crimes. Food chemistry, 432, 137191.

We have added this point to our literature survey in the Introduction (lines 113-114).

4. Line no 186; the author should mention the temperature at which the urine and blood samples were stored.

The temperature was 4 °C for both blood and urine. This information has been added to the Methods section.

5. The author must provide the instrumental specifications of UHPLC-MS/MS and GC-MS used in determining drugs in blood and urine samples within the main manuscript.

This has been added to the Methods section in the manuscript.

6. What is “IQR”? The author must furnish information regarding this term for better understanding of readers.

IQR, meaning interquartile range, has now been explained on the first use of the abbreviation in both the abstract and the main text.

7. The author must include the chromatograms in the main manuscript for the better understanding of the readers.

We thank the reviewer for the suggestion. As method development is not the primary focus of this article and the methods are used on a routine basis, we do not believe adding chromatograms from three different methods will add substantially to the understanding of the topic, but rather might divert focus.

REVIEWER #4:

The manuscript entitled “Drugs in blood and urine samples from suspected spiked drink victims: a prospective observational study from Oslo, Norway” describes an important subject.

We have proofread the manuscript again for English language improvement and made appropriate changes throughout. Furthermore, we have clarified the definitions (cf. our more specific responses below) and made an effort to focus the manuscript on the aim and improve the conclusion, along the lines suggested below.

It is unclear whether the purpose is to identify which substances are used in these cases or whether the purpose is to make a comparison of identified substances in blood and urine.

The purpose was to identify the substances used in these cases, with a special concern for the unreported drugs. We have clarified this in the Objectives section both in the abstract and the main text.

The authors are encouraged to include more relevant drug classes such as sedative antihistamines, antidepressants etc. to increase the value of the study.

We agree that including these drug classes would have increased the value of the study. Unfortunately, we did not analyze for these drugs.

Words/terms which advantageously could be rephrased/changed in the manuscript:

We have mainly kept to using the term “patients” but have made some changes to “individuals” or “victims” as suggested, or “people”.

• Rephrase the objectives where the sentence say “patients with suspected spiked drinks”. Maybe write suspected victims of drink spiking instead.

We have rephrased this to “patients suspecting exposure to spiked drinks”.

We have tidied up our use of these terms throughout the manuscript, including in the title, now consistently using drink spiking.

• Consider to rephrase “unreported drugs” as this in many sentences is confusing. Consider to use “additional drugs which was not self-reported”

To avoid confusion, we have now provided a definition of the term “unreported drugs” in the Objectives section of both the abstract and the main text.

We have removed spiked drinks from the key words and aligned the key words in the manuscript and the front template.

Selected comments

Abstract:

• In objectives please, clarify the aim of the study.

We have clarified the aim of the study, both in the abstract objectives and the main text objectives.

We have added an interpretation of the significance of the unreported drugs.

Introduction:

• The introduction should be shortened and focusing more on the aim of the study.

As suggested, we have shortened the Introduction, focusing more on the aim of the study.

Materials and methods:

• It is unclear whether the substances are only screened or whether they are also verified.

Whole blood samples were analyzed by specific methods with calibrators and internal standards in line with the common criteria for quantitative methods, but were only run once. Urine samples were screened with immunoassay, while GHB in urine was run quantitatively by GC-MS. We have rewritten the manuscript to make this clear to the reader.

• Include a more detailed description on the analytical methods used.

This has been included in the manuscript.

Result:

• Line 234 rephrase: we obtained biological samples in blood.

We have rephrased as suggested.

• Table 2: Misleading numbers in the table: is total number of cases in the reported and unreported 100 in each? while the total number is also 100.

We see that stating percentages of the total of all samples for both reported and unreported drugs did not work very well. We have changed our reporting in Table 2 as suggested.

• Table 3: Why mention the symptoms and clinical features if they are not used in the classification of "drink spiking".

We think describing the symptoms and clinical features substantiates the reasons the patients gave for suspecting drink spiking and gives an impression of the clinical picture in the presentations. Most of the symptoms and clinical features could also be due to the drugs and alcohol the patients stated they had taken. Hence, we would not expect much help from the symptoms and clinical features in discerning between having actually been exposed to drink spiking or not, cf. Table 1.

Discussion:

We have elaborated on this in the second paragraph in Discussion (lines 323-332). This paragraph was developed from the last paragraph in the Limitations section in the previous version of the manuscript, now moved to a more prominent place to underscore this important point.

• What can this study be used for? What do the reader achieve by reading the paper?

We hope to contribute to clinicians’ understanding of the complex question of suspected exposure to drink spiking. It is of serious concern to individuals thinking themselves possibly exposed. Laboratory testing can help to some extent, though limited analytical libraries and timing issues are a problem. Furthermore, drinks may be spiked with ethanol, or with a drug also taken voluntarily by the patient. Then, there is the possibility that the patient underestimates the effects of ethanol and/or drugs taken intentionally. All these factors should be considered when addressing the concern of the patient suspecting exposure to drink spiking. We have elaborated on these implications in a paragraph added to the Conclusion.

We agree that we cannot prove that ethanol was used for drink spiking in our study. We have tried to clarify this by moving the limitations paragraph on the problem of drugs we did not test for to the beginning of the Discussion (lines 323-332), by rephrasing parts of the ethanol paragraph (lines 375-391), and by elaborating on the unreported drugs found in the Conclusion.

We have removed the sentence about smoking, and we have toned down our claims on drink spiking with ethanol both in the ethanol paragraph in Discussion and in the Conclusion.

• Elaborate more on the ethanol results according to sampling time interval. Many of the samples were collected late, which could be the reason for lack of ethanol detection.

We have commented on this in the revised ethanol paragraph (lines 375-391).

Conclusion:

• What about the actual drug findings, these are not really elaborat

Attachment

Submitted filename: Response to reviewers.docx

pone.0306191.s003.docx^{(34.2KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0306191.r003

Decision Letter 1

Heather M Barkholtz

12 Jun 2024

Drugs in blood and urine samples from victims of suspected exposure to drink spiking: a prospective observational study from Oslo, Norway

PONE-D-23-26541R1

Dear Dr. Vallersnes,

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Reviewer #3: Yes

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Reviewer #3: Yes

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Reviewer #1: I have read your article and the responses to the inquiries from other reviewers with particular attention and interest. These inquiries are quite pertinent and have undoubtedly enriched the scientific content of your work. Personally, I find the impact of this study to be interesting and commend you for the scholarly presentation. In conclusion, the study certainly has interesting points as it addresses a topic of great interest. The objective is clear and adhered to. The main question addressed by the research is clear and entirely agreeable. I believe the information provided is sufficient and represents useful elements to encourage the development of new scientific work.

Reviewer #3: Manuscript Title: Drugs in blood and urine samples from victims of suspected exposure to drink spiking: a prospective observational study from Oslo, Norway

The authors have addressed my comments and now the manuscript can be accepted for publication.

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PLoS One. doi: 10.1371/journal.pone.0306191.r004

Acceptance letter

Heather M Barkholtz

17 Jun 2024

PONE-D-23-26541R1

PLOS ONE

Dear Dr. Vallersnes,

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 Checklist. STROBE statement—Checklist of items that should be included in reports of cross-sectional studies.

(DOC)

pone.0306191.s001.doc^{(81KB, doc)}

S1 File. S1 and S2 Tables.

Reporting limits in blood samples and cut-off values in urine samples.

(PDF)

pone.0306191.s002.pdf^{(99.9KB, pdf)}

Attachment

Submitted filename: Response to reviewers.docx

pone.0306191.s003.docx^{(34.2KB, docx)}

Data Availability Statement

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PERMALINK

Drugs in blood and urine samples from victims of suspected exposure to drink spiking: A prospective observational study from Oslo, Norway

Vivian M Dalaker

Håvard Furuhaugen

Mette Brekke

Mari Asphjell Bjørnaas

Maja Krpo

Elisabeth Leere Øiestad

Odd Martin Vallersnes

Roles

Abstract

Objective

Methods

Results

Conclusion

Introduction

Objectives

Materials and methods

Design

Setting

Inclusion

Data collection

Toxicological sampling and analyses

Outcome measures

Ethics

Study registration

Statistics

Results

Table 1. Reasons for suspecting exposure to drink spiking, symptoms at presentation, and clinical observations.

Fig 1. Blood ethanol concentration and time since suspected exposure to drink spiking.

Table 2. Substances found in blood and urine samples in patients suspecting exposure to drink spiking.

Table 3. Patients suspecting exposure to drink spiking, with drugs other than ethanol detected in blood and/or urine sample (n = 19).

Discussion

Possible drink spiking cases

Ethanol

Testing for drink spiking

Strengths and limitations

Conclusions

Supporting information

Acknowledgments

Data Availability

Funding Statement

References

Decision Letter 0

Miquel Vall-llosera Camps

Roles

Author response to Decision Letter 0

Decision Letter 1

Heather M Barkholtz

Roles

Acceptance letter

Heather M Barkholtz

Roles

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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