Enantiospecific gas chromatographic-mass spectrometric analysis of urinary methylphenidate: Implications for phenotyping
Enantiospecific gas chromatographic-mass spectrometric analysis of urinary methylphenidate: Implications for phenotyping
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DOI：
10.1016/j.jchromb.2007.11.030
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发表时间：
2008-02-01
影响因子：
3
通讯作者：
Patrick, Kennerly S.
中科院分区：
文献类型：
--
作者：
LeVasseur, Natalie L.;Zhu, Hao-Jie;Patrick, Kennerly S.
建立了一种手性衍生化气相色谱-质谱联用(GC-MS)分析尿中哌醋甲酯(MPH)的方法，并对一种新型MPH不良代谢物(PM)的初步研究结果进行了验证。通过电子轰击(EI)选择离子监测来自MPH的N-三氟乙酰丙基哌啶碎片和哌啶-氚的MPH内标进行检测。与10种正常MPH代谢物测定的平均值相比，PM在尿液中的排泄量接近70倍(0-10小时内剂量的9%)，d-异构体的排除量(剂量的10%)接近5倍。在PM和正常代谢者的尿液中只发现了少量的代谢物p-羟基-mph，而mph内酰胺的浓度还不够高，无法检测到。所描述的方法基于d-MPH：1-NWH的相对尿液浓度的评估，间接测量接受MPH的患者的功能羧酸酯酶-1状态。对已确诊或可疑的MPH PM的合理药物选择的临床意义进行了讨论。(C)2007 Elsevier B.V.保留所有权利。
A chiral derivatization gas chromatographic-mass spectrometric (GC-MS) method for urine methylphenidate (MPH) analysis was developed and validated to investigate preliminary findings regarding a novel MPH poor metabolizer (PM). Detection was by electron impact (EI) ionization-selected ion monitoring of the N-trifluoroacetylprolylpiperidinium fragments from MPH and the piperidine-deuterated MPH internal standard. The PM eliminated similar to 70 times more 1-MPH in urine (9% of the dose over 0-10 h), and similar to 5 times more of the d-isomer (10% of the dose), than the mean values determined from 10 normal metabolizers of MPH. Only minor amounts of the metabolite p-hydroxy-MPH were found in the urine of both the PM and normal metabolizers, while the concentration of MPH lactam was not high enough to be detectable. The described method indirectly gauges the functional carboxylesterase-1 status of patients receiving MPH based on the evaluation of relative urine concentrations of d-MPH:1-NWH. Clinical implications concerning rational drug selection for an identified or suspected MPH PM are discussed. (c) 2007 Elsevier B.V. All rights reserved.