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Conclusion Capillary electrophoresis offers the advantages of high efficiency separations (4), short analysis times, short equilibrium times when changing selector and low selector consumption (5-9). CE is also low risk in that there are no expensive HPLC columns that can be damaged and it offers a “green” alternative to HPLC with minimal solvent waste production. These factors combine to make chiral method development by CE rapid and cost effective when compared with other technologies.
Transfer of chiral CEmethodologies to quality control highlights the need for reproducibility in separation and assay robustness. Historically, cyclodextrins used for chiral analysis have been notorious for lot-to-lot variability (10-12). The reason was due primarily to themanufacturing intent of these reagents, typically produced in large scale for applications other than chiral analysis.
Figure 4. Citalopram (C) andMetabolites in 5% Gamma-HSCD Drug or Metabolite
Acebutolol
Adrenaline, Nor- (Norepinephrine) Aminorex, Cis-4-methyl- Amphetamine
Amphetamine, 2,3-Dimethoxy- Amphetamine, 2,4-Dimethoxy- Amphetamine, 2,5-Dimethoxy-
Amphetamine, 2,5-Dimethoxy-4-bromo- Amphetamine, 2,5-Dimethoxy-4-ethyl- Amphetamine, 2,5-Dimethoxy-4-methyl- Amphetamine, 2,5-Dimethoxy-4-propyl- Amphetamine, 2,6-Dimethoxy- Amphetamine, 3,4-Dimethoxy- Amphetamine, 3,5-Dimethoxy- Amphetamine, 3-Methoxy-4,
5-methylenedioxy- Amphetamine, N-Ethyl-
Amphetamine, 4-Methylthio- (4-MTA) Amphetamine, Hydroxy- Atenolol
Bisoprolol
Brompheniramine, Dinor- Brompheniramine, Nor- Bupropion
Bupropion, Erythroamino- Bupropion, Hydroxy-
Bupropion, Threoamino- Butriptyline, N-desmethyl- Chloroquine, N,N,-Didesethyl- Chloroquine, N-Desethyl- Chlorpheniramine
Chlorpheniramine, Dinor- Chlorpheniramine, Nor- Citalopram
CitalopramN-Oxide Citalopram, Dinor- Citalopram, Nor- Cyclazocine
Cyclobenzaprine
Cyclobenzaprine, N-Desmethyl- Desloratadine
Dihydro-N,N-dimethyl-5-methylene- ** Disopyramide, p-Cl
Disopyramide, N-Dealkylated- Doxapram Doxylamine
EDDP (MethadoneMtb.) EMDP (MethadoneMtb.) Ephedrine
Ephedrine, Hydroxy Esmolol
Fluoxetine
Resolution 2.4 3.5 4.5
33.2 16.6 22.5 17.2 9.9
11.6 13.8 6.0 4.5
14.4 4.6 4.6
14.7 13.4 30.6 3.4 2.2 0.8 1.0
10.1 7.5 6.3 7.6 1.1 1.9 1.1 2.5 1.0 1.1
11.1 11.0 8.0 8.0 3.8 1.9 5.4 6.4 3.2 4.7 4.6 7.2 2.2 3.0 7.5 6.1
15.6 3.1
12.0
System* Gamma
Gamma 2.5 Gamma Gamma Gamma Gamma Gamma Beta
Gamma Gamma Gamma Gamma Gamma Gamma Gamma
Gamma Gamma Gamma Gamma
Gamma 2.5 Beta 7.5 Beta
Alpha
Gamma Beta
Alpha Alpha
Gamma 7.5 Alpha
Beta 7.5 Beta 7.5 Beta 7.5 Gamma Gamma Gamma Gamma Beta
Gamma 7.5 Alpha
Gamma Alpha Beta
Alpha Gamma
Gamma 7.5 Beta 7.5 Gamma Alpha
Gamma Gamma Alpha 2.5
* All systems 5% unless indicated ** Dihydro-N,N-dimethyl-5-methylene-5H-dibenzocycloheptene-10-ethanamine, 10,11-” *** Compound with 2 chiral centers
Drug or Metabolite Fluoxetine, Nor- Glutethimide Ketamine
Ketamine, Nor- Labetolol MBDB
MDA, 2,3- MDA, 3,4- MDEA, 3,4- MDMA, 2,3- MDMA, 3,4- Methadone
Methamphetamine Methoxamine
Methylphenidate
Metoprolol Mexilitine Midazolam Mirtazapine
Mirtazepine, N-Desmethyl Nadolol
Nefopam
Oxprenolol Pentazocine Pheniramine
Phenmetrazine
Phenylephrine, N-Desmethyl- Phenylpropanolamine Pindolol
PMA (p-Methoxyamphetamine)
PMMA (p-Methoxymethamphetamine) Propranolol Pronethalol
Propoxyphene
Pseudoephedrine Quetiapine Quinidine Salbutamol Tetramisole Tramadol
Tramadol, Nor- Trimipramine
Trimipramine, Nor- Venlafaxine
Venlafaxine,O-Desmethyl- Verapamil
Verapamil, Nor- Zopiclone
Zopiclone N-Oxide Zopiclone, Nor-
Resolution 9.8
11.8 2.2 4.5
16.7 14.6 7.1 9.7 7.8
26.6 11.8 44.4 14.5
4.2 2.7 3.1 5.4 7.5
10.0 7.2 2.8
19.5 3.6
42.6 2.0
25.3 13.1 4.3 2.5 7.3 5.2 4.4 2.3 8.3 3.6
13.3 10.3 7.3 2.0 5.5 4.3 7.1 6.9
24.0 23.6 31.6
System* Gamma Gamma Gamma Alpha
5.1/2.9/2.1*** Gamma 2.5 7.5
Gamma Gamma Gamma Gamma Gamma Gamma Beta
Gamma Gamma Gamma
Alpha 2.5
Gamma 7.5 Gamma Gamma Gamma
2.6/1.3/split*** Gamma 7.6
Alpha Beta
Gamma 7.5 Beta 7.5 Alpha Alpha
Gamma Beta 7.5 Gamma Gamma Alpha 2.5 Alpha 2.5 Alpha
Gamma Gamma Alpha Beta
Gamma Gamma Gamma Alpha Alpha
Gamma Gamma Alpha Alpha
Gamma Gamma Gamma
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