Maurer H H, Kraemer T
Abteilung Toxikologie, Universität des Saarlandes, Homburg, Federal Republic of Germany.
Arch Toxicol. 1992;66(9):675-8. doi: 10.1007/BF01981508.
Selegiline (R(-)-N-methyl-N-(1-phenyl-2-propyl)-2-propinylamine), a selective MAO-B inhibitor used as an antiparkinsonian, is excreted in urine as N-desmethyl selegiline (norselegiline), R(-)-methamphetamine (R(-)-MA), R(-)-amphetamine (R(-)-AM) and their conjugated p-hydroxy derivatives. We found that the fluorescence polarization immunoassays (FPIA) TDx amphetamine/methamphetamine II (AM/MA II) and TDx amphetamine class (AM class) lead to positive results for up to 2 days after a single oral dose of 10 mg selegiline (detection limit: 0.1 mg/l, each). Every urine specimen from long term selegiline patients (10 mg/day) showed positive TDx results during the selegiline regimen. Positive TDx results were confirmed using gas chromatography-mass spectrometry (GC-MS). Selegiline metabolites, particularly MA, could be detected in urine for up to 7 days after intake of a single oral dose of 10 mg selegiline (detection limit: 0.01 mg/l for MA and AM). Norselegiline, the only specific selegiline metabolite, was only detectable for about 12 h. Moreover, norselegiline was not detected in all urine samples from long term selegiline patients (10 mg/day). Since differentiation of selegiline intake from MA/AM abuse by detecting norselegiline was not possible in most cases, an enantioselective GC-MS procedure was developed. It allowed differentiation of the enantiomers of the selegiline metabolites and thereby separation of selegiline intake (only R(-)-enantiomers) from methamphetamine and/or amphetamine abuse (racemates or S(+)-enantiomers). After derivatization with S(-)-N-trifluoroacetyl-prolyl chloride (TPC), the two enantiomers of MA and AM were each separated as diastereomers employing the routinely used achiral GC capillary.(ABSTRACT TRUNCATED AT 250 WORDS)
司来吉兰（R(-)-N-甲基-N-(1-苯基-2-丙基)-2-丙炔胺）是一种用作抗帕金森病药物的选择性单胺氧化酶B（MAO-B）抑制剂，在尿液中以N-去甲基司来吉兰（去甲司来吉兰）、R(-)-甲基苯丙胺（R(-)-MA）、R(-)-苯丙胺（R(-)-AM）及其共轭对羟基衍生物的形式排泄。我们发现，荧光偏振免疫分析法（FPIA）TDx苯丙胺/甲基苯丙胺II（AM/MA II）和TDx苯丙胺类（AM类）在单次口服10 mg司来吉兰后长达2天会得出阳性结果（检测限：各为0.1 mg/l）。长期服用司来吉兰（10 mg/天）患者的每份尿液标本在服用司来吉兰期间TDx结果均为阳性。使用气相色谱-质谱联用仪（GC-MS）确认TDx结果为阳性。单次口服10 mg司来吉兰后，尿液中司来吉兰代谢物，尤其是MA，在长达7天内均可检测到（MA和AM的检测限：0.01 mg/l）。去甲司来吉兰是司来吉兰唯一的特异性代谢物，仅在约12小时内可检测到。此外，长期服用司来吉兰（10 mg/天）患者的所有尿液样本中均未检测到去甲司来吉兰。由于在大多数情况下无法通过检测去甲司来吉兰来区分司来吉兰的摄入与MA/AM滥用，因此开发了一种对映体选择性GC-MS方法。该方法能够区分司来吉兰代谢物的对映体，从而将司来吉兰的摄入（仅R(-)-对映体）与甲基苯丙胺和/或苯丙胺滥用（外消旋体或S(+)-对映体）区分开来。用S(-)-N-三氟乙酰基-脯氨酰氯（TPC）衍生化后，MA和AM的两种对映体各自作为非对映体通过常规使用的非手性GC毛细管进行分离。（摘要截短于250字）
