Baumann P, Bosshart P, Gabris G, Gastpar M, Koeb L, Woggon B
Clinique Psychiatrique Universitaire de Lausanne, Basle, Switzerland.
Arzneimittelforschung. 1988 Feb;38(2):292-6.
A gas chromatographic/mass spectrometric method (using either electron impact or chemical ionisation with methane or ammonia) is described for the quantitative analysis of maprotiline (MP, Ludiomil), N-acetylmaprotiline (AcMP) and N-acetyldesmethylmaprotiline (AcDMP) in whole blood or plasma. In two groups (A and B) of 82 and 53 depressive patients treated clinically with MP for 10 and 21 days, respectively, plasma and whole blood MP was monitored during the treatment. In group A, all subjects were phenotyped with debrisoquine and mephenytoin, and 44 with sulfamidine. 5 patients were poor metabolizers of debrisoquine and 2 of mephenytoin; 18 subjects were fast acetylators of sulfamidine. Traces of AcMP were found only in two patients. AcDMP was present in levels below 2 ng/ml in the plasma of most of the patients in group A. In group B, AcDMP levels between 2.4-14.6 ng/ml of whole blood were found in 9 patients. The mass spectral data suggest the presence of another, unknown MP metabolite interfering partly with the analysis of AcDMP. The presence of AcDMP seemed not to be related to the phenotype of the patients as determined by the pharmacogenetic tests.
本文描述了一种气相色谱/质谱法(采用电子轰击或甲烷或氨的化学电离),用于定量分析全血或血浆中的马普替林(MP,路滴美)、N - 乙酰马普替林(AcMP)和N - 去甲基乙酰马普替林(AcDMP)。在分别用MP临床治疗10天和21天的两组(A组和B组)抑郁症患者中,A组有82例,B组有53例,治疗期间监测了血浆和全血中的MP。在A组中,所有受试者都用异喹胍和美芬妥英进行了表型分析,44例用磺胺脒进行了分析。5例患者是异喹胍的慢代谢者,2例是美芬妥英的慢代谢者;18例受试者是磺胺脒的快乙酰化者。仅在两名患者中发现微量的AcMP。A组大多数患者血浆中AcDMP的水平低于2 ng/ml。在B组中,9例患者全血中AcDMP水平在2.4 - 14.6 ng/ml之间。质谱数据表明存在另一种未知的MP代谢物,部分干扰了AcDMP的分析。AcDMP的存在似乎与通过药物遗传学测试确定的患者表型无关。