Neugebauer M, Khedr A, el-Rabbat N, el-Kommos M, Saleh G
Pharmazeutisches Institut, University of Bonn, Germany.
Biomed Chromatogr. 1997 Nov-Dec;11(6):356-61. doi: 10.1002/(SICI)1099-0801(199711)11:6<356::AID-BMC692>3.0.CO;2-T.
Famprofazone (1) metabolites were studied in human urine after medication by 50 mg oral dose. The human urine was collected over 48 h from six volunteers at time intervals of 6, 12, 24 and 48 h. The amount of famprofazone metabolites were recovered from the urine samples by application of Extrelut extraction method. The resultant extracts were derivatized using N-methyl-N-trimethylsilytrifluoroacetamide (MSTFA) for trimethylsilylation followed by N-methyl-bis-trifluoroacetamide (MBTFA) for trifluoroacetylation. Methamphetamine (2) and 3-hydroxymethyl-propyphenazone (3), excreted in human urine, were identified as famprofazone metabolites by gas chromatography-mass spectrometry (GC-MS). The quantitative results revealed that the average amounts of 2 and 3, excreted in human urine were equal to 2.6 and 4 mg, respectively, through 48 h. However, 3 was analysed after enzymatic hydrolysis of the urine samples using beta-glucuronidase/arylsulphatase. The excreted methamphetamine enantiomers could be separated by application of indirect GC-technique using S-(-)-N-trifluoroacetylprolyl chloride (TPC) as a chiral derivatizing agent. The average amount of (-)-methamphetamine isomer excreted in the urine was found to be three fold those of the (+)-isomer.
在50毫克口服剂量给药后，对人尿液中的安替比林（1）代谢物进行了研究。在48小时内，每隔6、12、24和48小时从6名志愿者收集人尿液。采用埃特拉路特萃取法从尿液样本中回收安替比林代谢物的量。所得提取物先用N-甲基-N-三甲基硅基三氟乙酰胺（MSTFA）进行三甲基硅烷化衍生化，然后用N-甲基-双三氟乙酰胺（MBTFA）进行三氟乙酰化衍生化。通过气相色谱-质谱联用（GC-MS）将人尿液中排泄的甲基苯丙胺（2）和3-羟甲基-丙基安替比林（3）鉴定为安替比林代谢物。定量结果显示，在48小时内，人尿液中排泄的2和3的平均量分别为2.6毫克和4毫克。然而，3是在使用β-葡萄糖醛酸酶/芳基硫酸酯酶对尿液样本进行酶水解后进行分析的。通过使用S-（-）-N-三氟乙酰脯氨酰氯（TPC）作为手性衍生化剂的间接气相色谱技术，可以分离排泄的甲基苯丙胺对映体。发现尿液中排泄的（-）-甲基苯丙胺异构体的平均量是（+）-异构体的三倍。
