A method for the microdetermination of dihydroergotoxine (DHETX) levels in the human plasma by gas chromatography/high resolution-selected ion monitoring (GC/HRSIM)(M/ΔM=5000) has been investigated to study the pharmacokinetics of DHETX in man. Deuterium labelled dihydroergotamine was prepared by catalytic hydrogenation of ergotamine by deuterium gas and used as an internal standard for quantification.To the plasma was added [2H3] dihydroergotamine followed by extraction of DHETX by using ClinElut ®, and DHETX was hydrolysed to dihydrolysergic acid. Dihydrolysergic acid was analysed as its N-trimethylsilyl ethyl ester using the molecular ions with m/z 370.2076 and 373.2265. Thus, GC/HR-SIM made it possible to quantify selectively trace amounts of DHETX in the human plasma without interference of endogenous substances and/or silylating agent. Detection limit was 2 pg with S/N of 19, better than that of conventional GC/LR-SIM. Improvement of sensitivity in high resolution-mode may be attributable to enhancement of the S/N ratio in the detection of SIM.
