T. Alebickolbah et Ap. Zavitsanos, CHIRAL BIOANALYSIS BY NORMAL-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY-ATMOSPHERIC PRESSURE IONIZATION TANDEM MASS-SPECTROMETRY, Journal of chromatography, 759(1-2), 1997, pp. 65-77
Citations number
32
Categorie Soggetti
Chemistry Analytical","Biochemical Research Methods
A highly sensitive and specific chiral high-performance liquid chromat
ographic tandem mass spectrometric (HPLC-MS-MS) technique has been dev
eloped for the determination of several chiral drugs and their metabol
ites. Examples include enantiomers of verapamil and its most abundant
active metabolite, norverapamil, enantiomers of oxybutynin and its met
abolite, N-desethyloxybutynin, enantiomers of doxazosin and those of s
otalol. These drugs are marketed as racemates although their optical i
somers possess different pharmacological activities. Drug enantiomers
and their respective chiral metabolites were separated by isocratic no
rmal-phase chiral chromatography on a small-bore (100X2.1 mm I.D.) Chi
ralpak AD column. Post-column reagent addition of an aqueous mobile ph
ase was introduced to enable direct coupling of hexane-based mobile ph
ases chiral chromatography with the heated nebulizer interface of the
SCIEX API 300 tandem mass spectrometer. Quantification of individual d
rug and metabolite enantiomers was obtained by multiple reaction monit
oring. This novel approach was developed and used in bioanalytical stu
dies. It successfully combines the convenience of normal-phase chiral
separations on small-bore HPLC columns with high specificity and low l
imits of quantification achieved by atmospheric pressure ionization MS
-MS detection.