Quantitative determination of metformin, glyburide and its metabolites in plasma and urine of pregnant patients by LC-MS/MS.

Quantitative determination of metformin, glyburide and its metabolites in plasma and urine of pregnant patients by LC-MS/MS.
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DOI:
10.1002/bmc.3314
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发表时间:
2015-04
影响因子:
1.8
通讯作者:
Ahmed, Mahmoud S.
Ahmed, Mahmoud S.
中科院分区:
医学4区
文献类型:
--
作者:
Zhang, Xing;Wang, Xiaoming;Vernikovskaya, Daria I.;Fokina, Valentina M.;Nanovskaya, Tatiana N.;Hankins, Gary D. V.;Ahmed, Mahmoud S.

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本报告描述了用于定量测定接受两种药物联合治疗的妊娠患者血浆和尿液中格列本脲(GLB)、其5种代谢产物(M1、M2 a、M2 b、M3和M4)和二甲双胍(MET)的LC-MS/MS方法的开发和验证。血浆样品中分析物的提取回收率范围为87%-99%,尿液样品为85%-95%。分析物之间保留时间的差异以及患者血浆和尿液样本中药物及其代谢物的浓度范围广泛,需要开发三种LC方法。血浆样本中分析物的定量下限(LLOQ)如下:GLB,1.02 ng/mL;其5种代谢产物,0.100-0.113 ng/mL,MET为4.95 ng/mL。尿样中GLB的LLOQ为0.0594 ng/mL,其5种代谢产物的LLOQ为0.984-1.02 ng/mL,MET的LLOQ为30.0 μg/mL。该方法对血浆和尿液样品的日内和日间测定的相对偏差< 14%,血浆的准确度为86%~ 114%,尿液的准确度为94%~ 105%。本报告中描述的方法成功用于测定患者血浆和尿液中两种药物的浓度。
This report describes the development and validation of an LC-MS/MS method for the quantitative determination of glyburide (GLB), its five metabolites (M1, M2a, M2b, M3, and M4) and metformin (MET) in plasma and urine of pregnant patients under treatment with a combination of the two medications. The extraction recovery of the analytes from plasma samples ranged between 87% and 99%, and 85%–95% for urine samples. The differences in retention times among the analytes, and the wide range of the concentrations of the medications and their metabolites in plasma and urine patient samples required the development of three LC methods. The lower limit of quantitation (LLOQ) of the analytes in plasma samples was as follows: GLB, 1.02 ng/mL; its five metabolites, 0.100–0.113 ng/mL and 4.95 ng/mL for MET. LLOQ in urine samples was 0.0594 ng/mL for GLB, 0.984–1.02 ng/mL for its five metabolites and 30.0 μg/mL for MET. The relative deviation of this method was < 14% for intra-day and inter-day assays in plasma and urine samples, and the accuracy ranged between 86% and 114% in plasma, and 94% to 105% in urine. The method described in this report was successfully utilized for determining the concentrations of the two medications in patient plasma and urine.
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