Use of chiral liquid chromatography-tandem mass spectrometry to investigate the metabolism of racemic cholecystokinin-B antagonists.
In an attempt to establish the enantiomeric specificity of metabolism for a series of racemic cholecystokinin-B receptor antagonists, chiral LC-MS-MS conditions were established using a Pirkle DNBL chiral stationary phase operating in the reversed-phase mode. Rat liver microsomal incubations of the compounds were analysed using these conditions and it was demonstrated that resolution of oxygenated and demethylated metabolites could be achieved. A single model compound was investigated in detail by obtaining product-ion spectra on all mono-oxygenated species in an attempt to correlate these and identify enantiomeric pairs of metabolites. In this example a lack of differentiation in the product ion spectra did not allow correlation but the results suggest that such an approach may still be viable for the chiral metabolic analysis of racemic material.
Watt
A P
AP
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Hitzel
L
L
Morrison
D
D
Locker
K L
KL
D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism* / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D002853:Chromatography, Liquid / Q000379:methods*; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D013237:Stereoisomerism
D001569:Benzodiazepines; D002766:Cholecystokinin