Determination of acetyltrimoprostil and its metabolite trimoprostil in human or dog plasma by gas chromatography-negative-ion chemical ionization mass spectrometry.
A sensitive and specific procedure is described for the determination of the antisecretory prostaglandin acetyltrimoprostil and its metabolite trimoprostil in human or dog plasma using gas chromatography--negative-ion chemical ionization mass spectrometry (GC--NICI-MS). Trideuterated analogues of both compounds are added to plasma as the internal standards. The plasma is extracted at pH 7.3 with benzene--dichloromethane (9:1), and the residue of the organic extract is reacted at room temperature with pentafluorobenzyl bromide in the presence of 18-crown-6-ether and potassium acetate. The derivatives are reconstituted in heptane, and appropriate aliquots are analyzed by GC--NICI-MS with selected-ion monitoring of the intense (M--C6F5CH2)- fragment ions of acetyltrimoprostil (m/z 419), trimoprostil (m/z 377), and their respective trideuterated analogues (m/z 422 and m/z 380, respectively). Quantitation of an experimental plasma sample is based on a comparison of the m/z 419 versus m/z 422 and m/z 377 versus m/z 380 ion ratios in each sample to that obtained from the analysis of drug-free plasma fortified with various amounts of both protio compounds, and a fixed amount of each trideuterated internal standard. The limit of quantitation of the assay for human plasma is 0.2 ng ml-1 with mean relative standard deviations at this concentration of 15.5% and 9.7% for acetyltrimoprostil and trimoprostil, respectively.
D000818:Animals; D000897:Anti-Ulcer Agents / Q000097:blood*; D002849:Chromatography, Gas; D015232:Dinoprostone / Q000031:analogs & derivatives*; D004285:Dogs; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D011459:Prostaglandins E, Synthetic / Q000097:blood*; D013045:Species Specificity
D000897:Anti-Ulcer Agents; D011459:Prostaglandins E, Synthetic; C038879:trimoprostil; C044129:Ro 22-6923; D015232:Dinoprostone