Quality assessment of some specific drug products beyond expiration dates in Saudi Arabia

Abstract

This study investigates the stability of expired emergency medications, dopamine, dexamethasone, naloxone, epinephrine, and dobutamine, beyond their labeled expiration dates in Saudi Arabia. The research addresses a critical issue in healthcare, where short shelf lives lead to substantial medication waste and financial losses. Using validated HPLC methods compliant with USP and BP guidelines, we analyzed the active pharmaceutical ingredient (API) content of these medications post-expiry. Our methodology involved collecting expired samples from public hospitals, which were stored under controlled conditions (protected from light and maintained at a consistent temperature between 15 °C and 30 °C), and conducting physical and chemical analyses to assess their stability. The results indicate that naloxone, dexamethasone, and dobutamine may be viable candidates for shelf-life extension programs, as they retained their API content within acceptable limits. However, epinephrine and dopamine exhibited stability challenges, with significant degradation observed in some samples. The findings suggest that pharmaceuticals can remain effective longer than their expiration dates, potentially reducing waste and improving resource management. However, packaging materials and storage conditions are crucial for maintaining drug stability. This study contributes to the ongoing discussion on shelf-life extension and highlights the need for further research to validate these results across different brands and environmental conditions. The implications of this research are significant, as extending shelf lives could enhance drug availability and reduce shortages, particularly for critical emergency medications like naloxone. Future studies should focus on conducting long-term stability tests under various climatic conditions to support shelf-life extension initiatives effectively.

Introduction

A short expiration date of a drug can pose a significant challenge for hospitals, nursing homes, and governmental agencies that stockpile large quantities of medications. Many drugs stored in suitable conditions and kept in their original unopened containers retain about 90% of their potency for at least 5 years after the labeled expiration date, and sometimes much longer (Iserson 2021). A shelf-life of 1–5 years is typically assigned to the finished pharmaceutical products based on the results of the real-time (long-term) stability tests and the accelerated stability tests. Due to the high cost and time consuming of such studies, expiry dates are conservatively estimated by pharmaceutical manufacturers. The average shelf life of Saudi manufactured drugs and imported drugs where calculated and found to be 30.35 and 31.7 months, respectively (Alshehri et al. 2023). As noticed, the expiry dates are relatively short which might exacerbate massive medication and drug shortages wastage in Saudi market. Saudi Arabia spends billions to provide treatment while wasting medications results in a huge financial loss (Banjar et al. 2022). Drug shortage is defined as period of time when a drug is in shortage or unavailable because supply from the warehouses of the official agent does not meet the needs of the health facilities (SFDA 2022). Several factors would contribute to drug shortage such as failure to notify SFDA in advance of anticipated drug shortages, poor supply chain management systems, overdependence on prescription drug imports and low-profit margins of some essential drugs (Alruthia et al. 2018). However, several approaches have been utilized to overcome drug shortage and enhance global drug security (Aljadeed et al. 2021). Among these approaches are the localization and local manufacture of medicine to achieve self-sufficiency, Shelf-life extension Request Initiated by the Manufacturer, Emergency Use Authorities and Shelf-Life Extension Programs. The shelf life extension program (SLEP) is the federal, fee-for-service program through which the labeled shelf life of certain federally stockpiled medical materiel can be extended after select products undergo periodic stability testing conducted by FDA (FDA 2022). SLEP's data on 122 drug products since 1986 were reviewed and analyzed by Lyon and his colleagues in 2006. According to the incidence of initial extension failures and termination failures in retesting initially extended lots, the authors classified the drug products into five groups. As a result, 2650 (88%) of the 3005 lots were extended past their original expiration date for an average of 66 months (Lyon et al. 2006). Similarly, all stockpiled drug products have been subjected to long-term stability tests by the German military (Bundeswehr) in their laboratories under extreme climate conditions such as found in potential crisis areas around the world. It was reported that 25-year-old morphine autoinjectors had been stored under controlled conditions without losing their quality, according to a German journal of military medicine (Wehrmedizin and Wehrpharmazie). However, a high lot-to-lot variability was observed which necessitate periodic testing and systematic assessment of each lot when an extension of shelf-life is intended. Regarding manufacturers, a supplemental new drug application for Tamiflu® and Relenza® was approved in 2010 by FDA in response to seasonal flu and H1 N1. Both drug products were extended for a period of seven years following their manufacture dates (Zilker et al. 2019). Moreover, in anticipation of antiviral medication shortages in 2020, FDA extended the expiry dates of oseltamivir and zanamivir for 15 and 10 years, respectively (Iserson 2021). It is apparently observed upon review of previous data that some drug products can be extended past the original expiration date through testing programs of promising potential candidates. The world health organization (WHO) has published The core list which presents a list of minimum medicine needs for a basic health-care system, listing the most efficacious, safe and cost–effective medicines for priority conditions which are selected on the basis of current and estimated future public health relevance, and potential for safe and cost-effective treatment (Usp 2024). The list involves many drug classes including emergency medications. Furthermore, some emergency medications are in shortage as listed in SFDA website such as Naloxone, epinephrine, Dopamine, Dexamethasone and dobutamine. The absence of these drugs would adversely affect patients and the healthcare system. Extending the shelf life of pharmaceutical products has a positive impact on security of local medicines, so a study was needed to evaluate the stability profile of different types of expired pharmaceutical products in the Kingdom of Saudi Arabia, which is characterized by the diversity of its climate (Al-Aqeel et al. 2010).

This study aims to investigate the stability of expired emergency medications, dopamine, dexamethasone, naloxone, epinephrine, and dobutamine, beyond their labeled expiration dates in Saudi Arabia. These medications are crucial due to their clinical significance, the healthcare system's reliance on them, their shortage status in the Saudi market, and their potential for shelf-life extension programs. The research addresses the substantial medication waste and financial burdens resulting from short shelf lives, seeking to determine whether these medications retain their active pharmaceutical ingredient (API) content post-expiry. As there are no published studies on testing expired medicines in Saudi Arabia, this investigation is vital for optimizing pharmaceutical resource management and addressing drug shortages.

Materials and methods

Samples

During our research, we faced significant challenges in finding expired products (more than one lot for each expired product) in the market or hospitals. All tested samples were kindly donated from some hospitals which include:

• Samples of expired Naloxone hydrochloride injections, USP® 2 mg/2 ml in Prefilled Syringe by International Medication Systems (United States).

• A Sample of expired Dopamine hydrochloride 40 mg/ml injections in glass ampoules by Jazeera pharmaceuticals industries (Saudi Arabia).

• Samples of expired and unexpired batches of Dexamethasone sodium phosphate 8 mg/2 ml injections in Amber glass ampoules by Egyptian International Pharmaceutical Industries Company (EIPICO) (Egypt).

• Samples of expired products of Epinephrin (Adrenaline tartrate) injectable solution in different container closure systems including glass ampoules (Aronepâ) by Tabuk pharmaceutical manufacturing co (Saudi Arabia), prefilled syringes: 10,000 Epinephrine injections by Aurum Pharmaceuticals Limited (United Kingdom) and two batches of epinephrine injections 1:1000 in ampoules by Martindale pharmaceuticals limited (United Kingdom).

• A Sample of expired Dobutamine injections USP in amber ampoules by verve humancare lab (India).

Materials

USP Naloxone reference standard, USP Dopamine Hydrochloride RS, Dexamethasone sodium phosphate European Pharmacopeia (EP) Reference Standard, Betamethasone sodium phosphate European pharmacopeial standard, USP Methyl paraben standard, USP Propyl paraben standard, USP Epinephrine Bitartrate reference standard (RS), USP Norepinephrine Bitartrate RS, USP Adrenalone Hydrochloride RS and USP Dobutamine Hydrochloride RS by Sigma-Aldrich (Seelze, Germany). Sodium 1-octanesulfonate anhydrous, Citric acid and sodium hydroxide were obtained from Sisco research Laboratories Pvt. Ltd. (Maharashtra, India). Sodium chloride by Scharlab S.L. (Barcelona, Spain). Potassium Dihydrogen phosphate, Sodium Dihydrogen phosphate and Edetate Disodium by Panreac. (Barcelona, Spain). Methanol, Triethylamine, Acetonitrile, Hexylamine and Phosphoric acid by Fisher scientific (England, UK). Hydrochloric acid 37%, Glacial acetic acid and Ferric chloride by Sigma-Aldrich (Seelze, Germany). Water (HPLC grade) was provided by Milli-Q plus purification system (Billerica, MA, USA) available at site. All chemicals are analytical grade and solvents are HPLC grade.

Instrumentation

HPLC instrument equipped with a diode array detector (DAD)- (Shimadzu HPLC prominence- I LC- 2030,Japan) was used. Data processing was performed using LabSolutions software.For weighing, Toploader Balance by (Sartorius ENTRIS2201- Germany) and analytical Balance by (Mettler toledo XPE205, Switzerland).Micropipettes (10–100 μl) and (100–1000 μl) for dilution by (Glassco, India).For pH measurments, a pH meter by (Mettler toledo Seven Excellence, Switzerland) that was calibrated with buffers at pH 2, 4, 7 and 9.

Methods

Samples of expired Naloxone, Dopamine, Dexamethasone, Dobutamine and Epinephrine (protected from light and maintained at a consistent temperature between 15 °C and 30 °C) were examined physically for quality attributes of injectable solutions such as appearance, clarity, color, pH, and Chemical analysis of Naloxone, Dopamine, Dexamethasone, Dobutamine and Epinephrine were carried out by using stability-indicating, reverse-phase, High Performance Liquid Chromatography (HPLC) methods according to United State Pharmacopeia (USP) or British pharmacopeia (BP) (‘BP’, 2024). Sample preparation involved creating suitable dilutions to ensure all analyte concentrations were within the established linear ranges of their corresponding HPLC methods. To maintain analytical integrity, standard solutions were injected at the beginning and end of each sample set, confirming consistent chromatographic performance throughout the testing period. The entire analytical process, encompassing all sample evaluations, was conducted between February and June 2024, ensuring a consistent timeframe for data collection and analysis.

HPLC separations were carried out using multiple columns mentioned in each analytical method used as described in the Table below:

Active pharmaceutical Ingredient	Method Parameters
Naloxone	Mobile phase: A mixture of 1.36 g of sodium 1-octanesulfonate (anhydrous), 1.0 g of sodium chloride, 580 mL of water, 420 mL of methanol, and 1.0 mL of phosphoric acid Chromatographic system: Mode: LC Detector: UV 229 nm. For Identification B, use a diode array detector in the range of 200–400 nm Column: 4.6-mm × 25-cm; 5-µm packing L1 Flow rate: 1 mL/min Injection volume: 100 µL Pharmacopeia: USP (United States Pharmacopeia) Year: 2023
Dexamethasone Sodium Phosphate	Mobile phase: To 1.360 g of potassium dihydrogen phosphate add 0.600 g of hexylamine, mix, allow to stand for 10 min, dissolve in 182.5 mL of water, add 67.5 mL of acetonitrile, mix and filter (0.45 µm) Chromatographic system: Column: Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography R (5 µm) (Hypersil ODS is suitable) Flow rate: 1 mL per minute Detector: Use a detection wavelength of 254 nm Injection volume: 20 µL Pharmacopeia: EP (European Pharmacopeia) Year: 2023
Dopamine	Mobile phase: Acetonitrile and Solution A, (13:87) Solution A: 0.005 M sodium 1-octanesulfonate in 1% glacial acetic acid Chromatographic system: Mode: LC Detector: UV 280 nm Column: 4-mm × 30-cm; packing L1 Flow rate: 1.5 mL/min Injection volume: 40 µL Pharmacopeia: USP (United States Pharmacopeia) Year: 2023
Dobutamine	Mobile phase: Acetonitrile, methanol, and Ion-pair solution (28:14:58) Ion-pair solution: Dissolve 3.38 g of sodium 1-octanesulfonate in 1 L of water, and pipet 3 mL of triethylamine into the solution. Adjust the solution with phosphoric acid to a pH of 2.5 Chromatographic system: Mode: LC Detector: UV 280 nm Column: 4.6-mm × 25-cm; 5-µm, base deactivated packing L1 Flow rate:1 mL/min Injection volume: 20 µL Pharmacopeia: USP (United States Pharmacopeia) Year: 2023
Epinephrine	Mobile phase: To 1 L of 0.05 M monobasic sodium phosphate add about 519 mg of sodium 1-octanesulfonate and about 45 mg of edetate disodium, and mix. Adjust by the dropwise addition of phosphoric acid, if necessary, to a pH of 3.8. Mix 85 volumes of this solution with 15 volumes of methanol Chromatographic system: Mode: LC Detector: 280-nm detector Column: 4.6-mm × 15-cm column that contains packing L7 Flow rate: 2 mL/min Injection volume: 20 µL Pharmacopeia: USP (United States Pharmacopeia) Year: 2023

Results and discussion

Naloxone

Naloxone is A synthetic morphinane alkaloid. It is an opioid antagonist that is synthesized by replacing the methyl group (CH3) on the nitrogen (N) found in the structure of morphine with an allyl group (CH2 CH = CH2). It is a compound in the 4,5-epoxymorphinan series. As reported, the pH and oxygen contribute to the degradation of this class of compounds. The primary degradation product of Naloxone is 2,2′-dimer (Fig. 1) (Pruyn et al. 2019). At room temperature, alkaline and neutral solutions rapidly degrade, while acidic solutions are relatively stable. Degradation occurs most rapidly at elevated temperatures, especially when autoclaving is used. Naloxone stability has direct relationship to the amount of light exposed to it. It shows remarkable degradation under sunlight light exposure at room temperature (Altannak 2015).

Fig. 1.

Chemical structure of Naloxone and it’s related impurity

Three expired samples of Naloxone hydrochloride injection, USP® prefilled syringe by International Medication Systems (United States) were examined physically and pH value was measured. Furthermore, the naloxone content was analyzed and compared to naloxone reference standard (Fig. 2). The three tested samples were injected three times and it complied with acceptance criteria of naloxone content as stated in USP monograph of Naloxone Hydrochloride Injection (90.0%–110.0%) with 105.19%, 102.54% and 103.15. The Samples were tested for impurity 2,2′-binaloxone and the impurity peak was not observed in samples. Upon physical examination, the injectable solutions were clear and free from visible particles. Regarding pH measurement, all three sample has shown an acceptable value which complied with USP monograph of Naloxone Hydrochloride Injection (3.0–6.5). Our finding in (Table 1) has confirmed the outcome of SLEP report which state that Naloxone HCl injectable solution is a potential candidate for Extension program of expiry date. However, additional samples of different brand are needed to have more comprehensive data regarding the stability of expired Naloxone injectable solutions in Saudi Arabia.

Fig. 2.

Chromatograms of (a) Blank injection, (b) Naloxone Standard 10 μg/ml at 11.3 min, (c) Naloxone impurity (2,2′-binaloxone) at 22.1 min, (d) Naloxone HCl injection (Test 1) 10 μg/ml of naloxone, (e) Naloxone HCl injection (Test 2) 10 μg/ml of naloxone and (f) Naloxone HCl injection (Test 3) 10 μg/ml of naloxone

Table 1.

Summary of chemical and physical testes performed on three naloxone samples

Sample	Labeled expiry date	Test parameters	Result	Acceptance criteria
Test 1	6/2020	Appearance	Clear, free from particles	Clear, free from particles
		pH	3.861	(3.0–6.5)
		Assay of Naloxone	105.19%	(90.0%–110.0%)
		Impurity test	Not detected	No impurity detected
Test 2	6/2022	Appearance	Clear, free from particles	Clear, free from particles
		pH	3.657	(3.0–6.5)
		Assay of Naloxone	102.54%	(90.0%–110.0%)
		Impurity test	Not detected	No impurity detected
Test 3	7/2020	Appearance	Clear, free from particles	Clear, free from particles
		pH	3.811	(3.0–6.5)
		Assay of Naloxone	103.15%	(90.0%–110.0%)
		Impurity test	Not detected	No impurity detected

Dopamine

Dopamine hydrochloride is a compound named as 4-(2-aminoethyl)− 1, 2-benzenediol hydrochloride. Dopamine solutions are required to be stored at controlled room temperature and protected from excessive heat and from freezing. Dopamine is considered stable at pH 5 or below. Upon exposure to alkaline conditions, the catechol moieties are oxidized, cyclized, and polymerized to colored materials. The USP monograph of Dopamine HCl stated (Do not use the injection if it is darker than slightly yellow or discolored in any other way). The major Three degradation products of Dopamine and Dopamine related compound A, B and C (Fig. 3) (El-Sherbeni et al. 2020).

Fig. 3.

Chemical structure of Dopamine and its related impurities

Expired batch of Domine® 40 mg/ml concentrate for solution for infusion by Hikma italia SPA (Italy) was tested. Physical examination and pH measurement was performed. Then, The Dopamine HCl content was analyzed and compared to Dopamine HCl reference standard (Fig. 4). The tested sample was injected three times and it complied with acceptance criteria of Dopamine content as stated in USP monograph of Dopamine HCl Injection (95.0%–105.0%) with 101.28%. However, a minor degradation peak was observed in sample chromatogram which was accurately quantified by testing the presence of impurities (Fig. 5). The UV spectrum of obtained impurity peak was compared with saved spectrum in library but no identical spectrum has shown. Depending on relative retention time of impurities in USP, the unknown impurity peak percent (4.05%) is higher than unspecified impurity limit in USP monograph of Dopamine HCl which is (0.1%). Consequently, impurity limit test of dopamine injections is failed. Upon physical examination, the injectable solutions were clear, colorless and free from visible particles. Regarding pH measurement, the sample has shown an acceptable value which complied with USP monograph of Dopamine HCl Injection (2.5–5.0). Dopamine HCl injections was not included in SLEP program. Hence, the outcome of analytical testing of dopamine injections in (Table 2) has revealed that dopamine needs more stringent testing on more batches of Dopamine injections to illustrate the suitability of dopamine for expiry date extension program.

Fig. 4.

Chromatograms of Dopamine hydrochloride standard 0.16 mg/ml at 8.3 (a) and Dopamine hydrochloride injections 0.16 mg/ml at 8.3 (b)

Fig. 5.

Chromatograms of (a) Dopamine hydrochloride standard (0.16 mg/ml) at 3.9 and (b) Dopamine hydrochloride injections (0.16 mg/ml) at 3.9

Table 2.

Result of dopamine samples

Sample	Labeled expiry date	Test parameters	Result	Acceptance criteria
Domine sample	01/2022	Appearance	Clear, colorless and free from particles	Clear, free from particles
		pH	3.442	(2.5–5.0)
		Assay of Dopamine	101.28%	(95.0%–105.0%)
		Impurity test	4.05%	0.1%

Dexamethasone

Dexamethasone Sodium Phosphate (DSP) is an inorganic ester of dexamethasone (Fig. 6). DSP is preferably used in injectable solutions due to the poor aqueous solubility of dexamethasone. DSP solutions is light sensitive (AlAani and Alnukkary 2016). Two batches of Dexamethasone sodium phosphate injectable solutions by EIPICO (Egypt) was tested. The first batch was expired while the other batch is not. Physical examination and pH measurement was performed. Then, Dexamethasone sodium phosphate content was analyzed and compared to DSP reference standard (Fig. 7). The expired batch was injected three times and it complied with acceptance criteria of DSP content as stated in British pharmacopeial (BP) monograph of dexamethasone sodium phosphate (97.0%–103.0%) with 98.48%. Similarly, the content of DSP in Unexpired batch is 100.26%. Multiple peaks other than DSP were detected in the chromatograms at 8.852 min and at 34.783 min. Therefore, UV spectrum of detected peaks was compared with the saved spectrum in the library of HPLC instrument. An identical spectrum of methyl paraben and propyl paraben is confirmed of two peaks in sample chromatogram (Fig. 8). Accordingly, solutions of both methyl paraben standard and propyl paraben standard were injected to verify its presence in sample tested. the resultant chromatograms confirmed the identity of detected peaks in samples (Fig. 9). Methyl paraben and propyl paraben are preservatives in DSP injections. Upon physical examination, the injectable solutions were clear and free from visible particles. Regarding pH measurement, the two sample has shown an acceptable value which complied with BP monograph of dexamethasone sodium phosphate (7.5–9.5). Our finding in (Table 3) has confirmed the outcome of SLEP report which state that dexamethasone sodium phosphate solution is a potential candidate for Extension program of expiry date (Buga et al. 2021). However, additional samples of different brand are needed to have more comprehensive data regarding the stability of expired dexamethasone sodium phosphate injectable solutions in Saudi Arabia.

Fig. 6.

Chemical structure of dexamethasone sodium phosphate and it’s related impurities

Fig. 7.

Chromatograms of (a) DSP standard (12 µg/mL) at 18.1 and (b) Expired DSP injections (12 µg/mL) at 18.1 (c) Unexpired DSP injections (12 µg/mL) at 18.1

Fig. 8.

UV spectrum of (a) methyl paraben and (b) propyl paraben

Fig. 9.

Chromatograms of (a) methyl paraben (20 µg/mL) and (b) propyl paraben (30 µg/mL)

Table 3.

Result of dexamethasone sodium phosphate samples

Sample	Labeled expiry date	Test parameters	Result	Acceptance criteria
Test 1	01/2022	Appearance	Clear, colorless and free from particles	Clear, free from particles
		pH	7.57	(7.5–9.5)
		Assay of DSP	98.48%	(97.0%–103.0%)
		Impurity test	Not detected	No impurity detected
Test 2	01/2024	Appearance	Clear, colorless and free from particles	Clear, free from particles
		pH	7.58	(7.5–9.5)
		Assay of DSP	100.26%	(97.0%–103.0%)
		Impurity test	Not detected	No impurity detected

Epinephrine

Epinephrine belongs to Catecholamines group which degrade rapidly via oxidative reactions which are catalyzed by oxygen, pH > 6, heavy metal ions, heat and UV–Vis. Depending on the amount of antioxidative agent (e.g. sodium metabisulfite), pH, and type of container, Epinephrine injection solutions may degrade differently. As reported, Elevated temperatures and especially exposure to mixed daylight significantly decreased the shelf life of Epinephrine injections. The main impurities associated with Epinephrine Bitartrate are norepinephrine, (Fig. 10). Adrenalone and Unidentified impurity peak 1 (Unknown structure, and identified based on relative retention time) (Heeb et al. 2017).

Fig. 10.

Chemical structure of epinephrine bitartrate and its related impurities

Four expired samples of Epinephrine injectable solution in different container closure system were tested. Prefilled syringe of 1:10,000 Epinephrine injections by Aurum Pharmaceuticals Limited (United Kingdom), Aronep ampoules by Tabuk pharmaceutical manufacturing co. (Saudi arabia), two batches of epinephrine injections 1:1000 in ampoules by Martindale pharmaceuticals limited (United Kingdom). Physical examination and pH measurement was performed. then, the epinephrine content was analyzed and compared to epinephrine bitartrate reference standard (Fig. 11) where samples were injected three times. The epinephrine content of prefilled syringe, Aronep ampoules, epinephrine injections 1:1000 in ampoules batch 1 and batch 2 are 63.28%, 79.97%, 83.07% and 72.71%, respectively. additional peaks were detected in some samples chromatograms which indicate degradation of epinephrine. Upon physical examination, the injectable solutions were clear, colorless (not pinkish) and free from visible particles. Regarding pH measurement, all samples has shown an acceptable value which complied with USP monograph of Epinephrine (2.2–5.0). Based on our findings in (Table 4), Epinephrine injectable solution is a critical product which stability doesn’t support the decision of extending its expiry date. However, the different packaging materials of tested sample have illustrated that light resistant protection of solution is an essential factor to consider in epinephrine injections. As a result of the degradation behavior of epinephrine in pharmaceutical formulations, it is possible to prevent degradation by using light-resistant packaging, nitrogen used for the removal of oxygen from the ampoules, close pH control, preservatives added, and storage at low temperatures (Quarry et al. 2002).

Fig. 11.

Chromatograms of (a) Epinephrine Standard, 0.1 mg/ml at 5.8 min, (b) Prefilled syringe (Test 1), 0.1 mg/ml at 5.8 min, (c) Aronep ampoules, 0.1 mg/ml (Test 2) at 5.8 min, (d) Martindale ampoules batch 1, 0.1 mg/ml. (Test 3) at 5.8 min and (e) Martindale ampoules batch 2, 0.1 mg/ml. (Test 4) at 5.8 min,

Table 4.

Results of epinephrine samples

Sample	Labeled expiry date	Test parameters	Result	Acceptance criteria
Test 1	04/2022	Appearance	Clear, colorless and free from particles	Clear, free from particles
		pH	3.164	(2.2–5.0)
		Assay of Epinephrine	63.28%	(90%− 115%)
		Impurity test	Degradation peaks were detected	No impurity detected
Test 2	02/2023	Appearance	Clear, colorless and free from particles	Clear, free from particles
		pH	3.111	(2.2–5.0)
		Assay of Epinephrine	79.97%	(90%− 115%)
		Impurity test	Degradation peaks were detected	No impurity detected
Test 3	02/2022	Appearance	Clear, colorless and free from particles	Clear, free from particles
		pH	3.337	(2.2–5.0)
		Assay of Epinephrine	83.07%	(90%− 115%)
		Impurity test	Degradation peaks were detected	No impurity detected
Test 4	11/2022	Appearance	Clear, colorless and free from particles	Clear, free from particles
		pH	3.311	(2.2–5.0)
		Assay of Epinephrine	72.71%	(90%− 115%)
		Impurity test	Degradation peaks were detected	No impurity detected

Dobutamine

It is a synthetic catecholamine with activity at both alpha and beta adrenoceptors. It has been reported that the drug is rapidly broken down under basic conditions to form brown colored polymers via complex chemical pathways. Although dobutamine is stable in acidic conditions, it is susceptible to (Fig. 12) degradation in light (Mraz and Rorabaugh 2007).

Fig. 12.

Chemical structure of Dobutamine HCl and its related impurities

One expired sample of Dobutamine injections USP in amber ampoules by Verve humancare lab (India) was tested. Physical examination and pH measurement was performed. Then, Dobutamine content was analyzed and compared to Dobutamine HCl reference standard (Fig. 13). The tested sample was injected three times and it was complied with acceptance criteria of Dobutamine content as stated in USP monograph of Dobutamine Injection (90%—110%) with 102.25%. Upon physical examination, the injectable solutions were clear, colorless and free from visible particles. Regarding pH measurement, the sample has shown an acceptable value which The tested sample was complied with USP monograph of Dobutamine Injection (2.5–5.5).

Fig. 13.

Chromatogram of (a) Dobutamine HCl standard 0.5 mg/ml at 5.3 and (b) Dobutamine test 0.5 mg/ml at 5.3

Dobutamine HCl injections is categorized in Group1 C in SLEP report which means that tested lots of dobutamine are stable after expiry date for about 47 months. Our findings in (Table 5) has confirmed that dobutamine HCl injections in amber ampoules is a possible candidate for extension programs of expiry date. However, additional samples of different brand are needed to have more comprehensive data regarding the stability of expired Dobutamine injections in Saudi Arabia.

Table 5.

Results of dobutamine sample

Test 1	01/2023	Appearance	Clear, colorless and free from particles	Clear, free from particles
		pH	3.32	(2.5–5.5)
		Assay of Dobutamine	102.25%	(90%—110%)
		Impurity test	No impurity detected	No impurity detected

Conclusion

Our study provides valuable insights into the stability of expired emergency medications in Saudi Arabia, specifically dopamine, dexamethasone, naloxone, epinephrine, and dobutamine. The results indicate that naloxone, dexamethasone, and dobutamine are potential candidates for shelf-life extension programs, as they retained their active pharmaceutical ingredient (API) content within acceptable limits post-expiry. However, epinephrine and dopamine showed stability challenges, underscoring the need for careful consideration of packaging materials to maintain their stability.

The practical implications of these findings are significant. By identifying medications that can remain effective beyond their labeled expiration dates, healthcare systems can optimize resource allocation and reduce unnecessary waste. This research contributes to ongoing efforts to enhance drug availability and security, particularly in regions with diverse climatic conditions like Saudi Arabia. Future studies should prioritize long-term stability testing under various environmental conditions to further validate these results and support effective shelf-life extension initiatives.

Author contribution

Haya Aljohar (HA) conceptualized the study, developed the methodology, and wrote the original draft. Ghadah Altoum (GA) and Shahad Alkarni (SA) performed the data collection and analysis. Samiah Alhabardi (SA) verified the analytical methods and contributed to the interpretation of results. Modhi Alburaidi (MA) supervised the project, provided critical feedback, and helped shape the research. All authors reviewed and edited the final manuscript.

Funding

Researchers Supporting Project (number RSPD2025R622), King Saud University, Riyadh, Saudi Arabia.

Data availability

The relevant figures will be supplied following a formal request.

Declarations

Ethics approval

Not applicable.

Competing interests

The author declares no conflict of interest.