Studies on Drug Metabolism by Gas Chromatography-Mass Spectrometry and it's Related Technique.

Abstract

GC/MS revealed that α-ecdysone is biosynthsized by the prothoratic glands. The characteristic reactions of derivatization for GC/MS was utilized to elucidate the structures of the rat urinary metabolites of Mydocalm, and the unexpected chain elongation metaolites of 5-(chlo-n-butyl)picolinic acid in a novel metabolic pathway. The stable isotope techniques were applied to measure exactly the pharmacokinetics (PK) of d-and l-chlorpheniramines (CPA) in human using a pseudoracemate of d-CPA-d6 and l-CPA d0, and to measure both PK and pharmacodynamics of glycerol trinitrate and it's two kinds of dinitrates in dog and human. New silylating agents were synthesized and the resulted silyl ether derivatives of hydroxylated compounds provided some advantages for GC/MS. Furthermore, a new retention index, Δ [Um]E was defined by differences in the methylene unit values of the DMES and TMS ether derivatives, and was used for estimating the number of the hydroxyl groups. Alcoholic and phenolic hydroxyl groups in a compound was discrimated easily by the use of TMS-DMES exchange reaction. The profile analyses of biologically important substances were carried out by GC/MS for clarifing their physiological roles. The presence of PGD2 in human brain was identified and quantified by GC/HR/SIM using the Me-MO-DMiPS ether derivatives. The simultaneous determination of the activities of HMG-CoA reductase and cholesterol 7α-hydroxylase in human cauld be performed by quantifing the amounts of mevalonate and 7α-hydroxylcholesterol in plasma.