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. 2021 Aug 2;26(15):4681. doi: 10.3390/molecules26154681

Table 1.

Chiral CE methods for the analysis of pharmaceuticals developed by using experimental design strategies.

Analytes Sample Experimental Design Type Factors Responses Optimized Conditions References
Clenbuterol bulk substance PBD BGE pH, BGE concentration, CD concentration, methanol concentration, injection time resolution, migration time, number of theoretical plates 0.1 M citric acid/0.2 M phosphate BGE, pH 4.0, 16 mM β-CD, 19 °C, 13 kV, 214 nm [47]
Amlodipine bulk substance CCD BGE pH, CD concentration, temperature resolution, Kaiser peak separation function 50 mM phosphate BGE, pH 3.16, 18.2 mM α-CD, 17.2 °C, 25 kV, 214 nm [48]
Dexfenfluramine-chiral purity (levofenfluramine) bulk substance PBD BGE pH, CD concentration, methanol concentration, temperature, voltage resolution, migration time, peak symmetry 100 mM phosphate BGE, pH 3.0, 10 mM DM-β-CD, 40% methanol, 20 °C, 25 kV, 214 nm [50]
Amphetamines (amphetamine, methamphetamine, MDA, MDMA, MDEA) bulk substance CCD BGE concentration, BGE pH, CD concentration, temperature, voltage amphetamine resolution, total resolution, migration time, generated power 118 mM phosphate BGE, pH 3.5, 16 mM HP-β-CD, 28 °C, 25 kV, 200 nm [51]
Epinephrine bulk substance FrFD
CCD		 BGE concentration, BGE pH, CD concentration, temperature, voltage
BGE concentration, CD concentration, voltage		 resolution, migration time 111 mM phosphate BGE, pH 7.0, 9 mM CM-β-CD, 20 °C, 18 kV, 206 nm [52]
Imidazole derivatives (bifonazole, econazole, miconazole, sulconazole) bulk substance FrFD BGE pH, acetonitrile concentration, CD concentration, temperature resolution, migration time, number of theoretical plates 100 mM phosphate BGE, pH 4.70, 5.2% acetonitrile, 5.80 mM β-CD, 35 °C, 30 kV, 230 nm [53]
Celiprolol bulk substance, tablet, urine FCCD BGE concentration, BGE pH, CD concentration, temperature resolution, migration time, current 52 mM acetate BGE, pH 4.0, 3 mM S-β-CD, 19.5 °C, 30 kV, 220 nm [55]
Salbutamol spiked urine PBD
DD		 BGE concentration, BGE pH, CS concentration, methanol concentration, voltage
BGE pH, CS concentration, voltage		 resolution, migration time 30 mM Tris BGE, pH 5.3, 1.75% dermatan sulphate, 5% methanol, 15 °C, 24 kV, 220 nm [59]
Atropine ophthalmic solution, plant extract CCD BGE concentration, BGE pH, CD concentration resolution, migration time, current 55 mM phosphate BGE, pH 7.0, 2.9 mM S-β-CD, 20 °C, 20 kV, 195 nm [60]
Methadone bulk substance FFD
FCCD		 CD concentration, percentage of capillary filled with CD, gas nebulization pressure resolution CE-ESI-MS: 20 mM ammonium acetate BGE, pH 4.0, 18 mg/mL HP-β-CD/ 0.25 mg/mL CM-β-CD/ 0.4 mg/mL SBE-β-CD, 90/70/90% capillary-filled, nebulization pressure 2 psi [110]
Lactic acid body fluids (plasma, urine, amniotic and cerebrospinal fluid) FFD
FFD		 BGE concentration, BGE pH, CS concentration
BGE concentration, CS concentration		 resolution 200 mM phosphate BGE, pH 6.0, 413 mM HP-β-CD, 20 °C,−20 kV, 200 nm [63]
Propranolol bulk substance FCCD BGE concentration, BGE pH, acetonitrile concentration effective mobility, efficiency, symmetry, selectivity, relative mobility difference, resolution, difference in effective mobility 15 mM bistris-acetate, pH 6.5, 31.2 µM Cel7A, 17% (v/v) acetonitrile, 22 °C, 20 µA, 200 nm [64]
2-[(4′-benzoyloxy-2′-hydroxy)phenyl-propionic acid] bulk substance CCD CS concentration, BGE pH, temperature resolution, migration time 50 mM Britton-Robinson BGE, pH 6.4, 7 mM vancomycin, 22 °C, 20 kV, 195 nm [65]
Ofloxacin bulk substance FCCD BGE concentration, BGE pH, CD concentration, temperature resolution, migration time, peak area, current 50 mM phosphate BGE, pH 2.8, 4% (w/v) M-β-CD, 25 °C, 20 kV, 280 nm [66]
Ketamine injection solution PBD
CCD		 BGE concentration, BGE pH, CD concentration, methanol concentration, voltage
BGE pH, methanol concentration		 resolution 50 mM phosphate BGE, pH 5.20, 2% (w/v) CM-β-CD, 30% methanol, 20 °C, 15 kV, 206 nm [67]
Tamsulosin bulk substance BBD
FCCD
CCC		 CD concentration, voltage, temperature resolution, migration time 100 mM Tris BGE, pH 2.5, 0.15% (w/v) S-β-CD, 25 °C, 25 kV, 210 nm [75]
Risperidone, 9-hydroxyrisperidone bulk substance CCD CD1 concentration, CD2 concentration, BGE concentration resolution, migration time, selectivity, number of theoretical plates 80 mM phosphate BGE, pH 2.5, 37 mM HP- β-CD, 3.7% S-α-CD, 25 °C, 20 kV, 270 nm [76]
S-Citalopram--chiral purity (R-Citalopram) bulk substance, tablets FCCD BGE concentration, CD2 concentration, voltage, temperature resolution, migration time, current 20 mM phosphate BGE, pH 2.5, 0.5 mg/mL β-CD, 22 mg/mL S-α-CD, 28 °C, −20 kV, 205 nm [77]
Propranolol, 4-hydroxypropranolol bulk substance BBD BGE concentration, BGE pH, CD concentration, voltage resolution, migration time 25 mM triethylamine/phosphate BGE, pH 9.0, 4% (w/v) CM-β-CD, 25 °C, 17 kV, 208 nm [78]
Zopiclone bulk substance, tablets FFD BGE concentration, BGE pH, CD concentration, voltage resolution, migration time 60.2 mM phosphate BGE, pH 2.0, 1 M urea, 20 mM β-CD, 25 °C, 30 kV, 215 nm [79]
Clopidogrel (chiral purity R-clopidogrel) bulk substance reduced CCD BGE concentration, BGE pH, CD concentration, voltage resolution, migration time 10 mM triethylamine–phosphoric acid BGE, pH 2.3, 5% S-β-CD, 20 °C, −12 kV, 195 nm [80]
Dapoxetine bulk substance OAD BGE concentration, BGE pH, CD concentration, methanol concentration, temperature, voltage resolution 70 mM acetate BGE, pH 4.5, 3 mM M-γ-CD, 20% (v/v) methanol, 15 °C, 15 kV, 215 nm [82]
Magnesium-L-aspartate (chiral purity D-aspartate) bulk substance, tablets FFD BGE concentration, BGE pH, CD concentration resolution, migration time 50 mM phosphate, pH 7, 18 mM HP-β-CD, 18% (v/v) DMSO, 20 °C, 30 kV, LIF detection [87]
Asenapine bulk substance OAD BGE concentration, BGE pH, CD concentration, methanol concentration, temperature, voltage resolution 160 mM Tris-acetate BGE, pH 3.5, 7 mM β-CD, 20 °C, 15 kV, 214 nm [89]
Pomalidomide bulk substance OAD BGE concentration, BGE pH, temperature, voltage resolution 50 mM Tris-acetate BGE, pH 6.5, 15 mM CM-β-CD, 20 °C, 15 kV, 215 nm [90]
Lenalidomide (chiral purity R-lenalidomide) bulk substance FCCD BGE concentration, temperature, voltage resolution 30 mM phosphate BGE, pH 6.5, 30 mM SBE-β-CD, 10 °C, 12 kV, 210 nm [91]
Vildagliptin (chiral purity R-vildagliptin) bulk substance, tablets OAD BGE concentration, BGE pH, CD concentration, temperature, voltage, injection parameters resolution 75 mM Tris-acetate BGE, pH 4.75, 20 mM SBE-α-CD, 15 °C, 25 kV, 40 mbar × 4 s hydrodynamic injection, 200 nm [92]
Levosulpiride, (chiral purity R-sulpiride) bulk substance, tablets Asymmetric screening matrix
DD		 BGE concentration, BGE pH, type of neutral cyclodextrin, charged CD concentration, neutral CD concentration, voltage
BGE pH, charged CD concentration, neutral CD concentration, voltage		 resolution, migration time 5 mM Britton-Robinson BGE, pH 3.45, 10 mM S-β-CD, 34 mM M-β-CD, 16 °C, −14 kV, 214 nm [88]
Ambrisentan (chiral purity R-ambrisentan) bulk substance, coated tablets Asymmetric screening matrix
FCCD		 BGE concentration, BGE pH, CD concentration, SDS concentration, temperature, voltage, capillary length
BGE pH, CD concentration, voltage		 resolution, migration time capillary total length 64.5 cm, 100 mM borate BGE, pH 9.20, 100 mM SDS, 50 mM γ-CD, 22 °C, 30 kV, 200 nm [112]
S-Ambrisentan (chiral purity R-ambrisentan) bulk substance FrFD
FCCD		 concentration, BGE pH, CD concentration, temperature, voltage
BGE concentration, temperature, voltage		 resolution, migration time 50 mM sodium acetate BGE, pH 4.0, 30 mM γ-CD, 25 °C, 25 kV, 200 nm [93]
Montelukast (chiral purity R-trans-montelukast, R,S-cis-montelukast, S,R-cis-montelukast) bulk substance, chewable tablets, oral granules FFD BGE concentration, voltage resolution 20 mM borate BGE, 10 mM SDS, pH 9.0, 10 mM HTM-β-CD, 12 mM SBE-β-CD, 15 °C, 18 kV, 254 nm [113]
Levomepromazine (chiral purity R-mepromazine) bulk substance, injection solution FrFD
FCCD		 BGE concentration, BGE pH, CD concentration, temperature, voltage
BGE concentration, BGE pH, CD concentration		 resolution, migration time, selectivity 100 mM citric acid BGE, pH 2.85, 3.6 mg/mL HP-γ-CD, 15 °C, 25 kV, 253 nm [114]
S-Dapoxetine (chiral purity R-Dapoxetine) bulk substance, tablets FrFD
FCCD		 BGE concentra-tion, BGE pH, CD1-CD2 1:1 mix concentration, temperature, voltage
CD1 concentra-tion, CD2 concentration, voltage		 resolution, migration time, peak symmetry, current 50 mM phosphate BGE, pH 6.3, 45 mg/mL S-γ-CD, 40.2 mg/mL DM-β-CD, 15 °C, 9 kV, 215 nm [83]
Sitafloxacin, chiral impurities bulk substance FrFD
FCCD		 BGE concentration, BGE pH, CD concentration, Cu2+ concentration, D-Phe concentration, temperature, voltage
BGE pH, CD concentration, Cu2+ concentration, D-Phe concentration		 resolution, migration time 15 mM phosphate BGE, pH 4.5, 15 mM D-Phe, 20 mM CuSO4, 20 mM γ-CD, 25 °C, 15 kV, 297 nm [94]
Fluoxetine bulk substance, tablets OAD BGE concentration, BGE pH, CD concentration, temperature, voltage, injection parameters resolution 50 mM phosphate BGE, pH 5.0, 10 mM HTM-β-CD, 15 °C, 20 kV, 50 mbar × 1 s hydrodynamic injection, 230 nm [95]
Pregabalin bulk substance, capsules D-oD
FCCD		 BGE concentration, BGE pH, CD concentration, temperature, voltage
CD concentration, temperature, voltage		 resolution, migration time 100 mM phosphate BGE concentration, pH 2.5, 40 mg/mL HTM-β-CD, 25 °C, 15 kV, 220 nm [96]
Dexmedetomidine (chiral purity R-medetomidine) bulk substance, tablets FrFD
FCCD		 BGE concentration, BGE pH, CD concentration, temperature, voltage
CD concentration, temperature, voltage		 selectivity, migration time, current 50 mM phosphate BGE, pH 6.5, 40 mg/mL S-β-CD, 17 °C, 10 kV, 200 nm [97]
Dextrometorphan (chiral purity R-metorphan) bulk substance, tablets FrFD
FCCD		 BGE concentration, BGE pH, CD concentration, temperature, voltage
CD concentration, voltage		 resolution, migration time 30 mM phosphate BGE, pH 6.5, 16 mg/mL S-β-CD, 14 mg/mL M-α-CD, 20 °C, 20 kV, 200 nm [98]
Cinacalcet (chiral purity S-cinacalcet) bulk substance, tablets BBD BGE pH, CD concentration, methanol concentration, voltage resolution, migration time 150 mM phosphate BGE, pH 2.7, 3.1 mM HP-γ-CD, 2% (v/v) methanol, 18 °C, 26 kV, 220 nm [99]
Benzodiazepines (lorazepam, lormetazepam, oxazepam, temazepam) bulk substance FrFD BGE pH, CD type, CD concentration, methanol concentration resolution 20 mM borate BGE, pH 9.0, 5% HES-β-CD, 15% methanol, 15 °C, 20 kV, 230 nm [100]
Lansoprazole, Rabeprazole bulk substance, capsules FrFD
CCD		 BGE concentration, BGE pH, CD1 concentration, temperature, voltage
CD1 concentration, voltage, temperature		 resolution, migration time Lansoprazole: 25 mM phosphate BGE, pH 7.0, 10 mM SBE-β-CD, 20 mM γ-CD, 17 °C, 20 kV, 210 nm Rabeprazole: 25 mM phosphate BGE, pH 7.0, 15 mM SBE-β-CD, 30 mM γ-CD, 18 °C, 20 kV, 210 nm [104]
Levodropropizine (chiral purity R-dropropizine) bulk substance, pharmaceutical drops FFD
FCCD		 CD concentration, temperature, voltage, 2-propanol concentration
CD concentration, temperature		 separation factors, migration time, current 25 mM phosphate BGE, pH 7.0, 23.5 mg/mL S-β-CD, 10% (v/v) 2-propanol, 16.3 °C, 16.5 kV, 200 nm [106]
Levomepromazine (chiral purity R-mepromazine) bulk substance, tablets FrFD
FCCD		 BGE concentration, CD concentration, temperature, voltage
BGE concentration, CD concentration, temperature		 resolution, migration time, current 750 mM acetic acid, 55 mM ammonium acetate in methanol BGE, 27.5 mg/mL HDMS-β-CD, 15 °C, 22 kV, 250 nm [120]
Tramadol bulk substance, capsules FCCD BGE pH, CD concentration, temperature resolution, migration time 25 mM tetraborate BGE, pH 11.0, 5 mM CM-β-CD, 15 °C, 17.5 kV, 210 nm [105]
Amlodipine bulk substance, tablets OAD BGE concentration, BGE pH, CD concentration, temperature, voltage, injection parameters resolution 25 mM phosphate BGE, pH 9.0, 15 mM CM-β-CD, 15 °C, 25 kV, 30 mbar × 1 s hydrodynamic injection, 230 nm [107]
Citalopram bulk substance, tablets FrFD
FCCD		 BGE concentration, BGE pH, CD concentration, temperature, voltage, injection pressure
CD concentration, temperature, voltage		 resolution, migration time 25 mM phosphate BGE, pH 7.0, 3 mM CM-β-CD, 17.5 °C, 15 kV, 50 mbar injection pressure, 230 nm [108]
Venlafaxine bulk substance, capsules FCCD CD concentration, temperature, voltage resolution, migration time 25 mM phosphate BGE, pH 2.5, 10 mM CM-β-CD, 15 °C, 25 kV, 230 nm [109]