同位体分離法による合成麻薬性鎮痛薬フェンタニルの同位体希釈分析法の開発とその応用

概要

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Advantages of isotope dillution analysis for fentanyl (FT) and its main metabolite, norfentanyl (Nor-FT) were demonstrated. Isotopic fractionation for isotope dillution analysis was examined by separation of FT and its deuterated analogue using capillary gas chromatograph. The separation of FT and seven kinds of deuterated FTs were proportional to the number of labeled deuterium atoms and inversely to the temperature of the column oven. The propionyl group was more effectively position of deuterium labeling for isotopic fractionation than anilino or phenylethyl groups. The quantitative determination of FT in serum and urine was examined by GC equipped with a surface ionization detector (SID) . For an analysis of Nor-FT -in urine, N-alkylation was necessary to detect sensitively by SID. Methyl derivative was selected from 3 kinds of N-alkyl derivatives to increase sensitivity and peak resolution, and to prevent interference with urinary compound. No endogenous compounds or concomitant drugs interfered with the detection of FT and Nor-FT in the serum or the urine of patients. Furthermore, pharmacokinetics of FT was solved with the present method by two-compartment model built into metabolic process.