LC-MS/MS quantification of ataluren and ataluren acyl glucuronide in human plasma/urine: application in clinical studies

被引：0

作者：

Kaushik, Diksha ^{[1
]}

Ma, Jiyuan ^{[1
]}

Gu, Guodong ^{[1
]}

Hwang, Seongwoo ^{[1
]}

Moon, Young-Choon ^{[1
]}

Kong, Ronald ^{[1
]}

机构：

[1] PTC Therapeut, South Plainfield, NJ 07080 USA

来源：

BIOANALYSIS | 2020年 / 12卷 / 21期

关键词：

ataluren; glucuronide metabolites; human plasma; human urine; LC-MS; MS; method validation; quantification;

D O I：

10.4155/bio-2020-0214

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Background:This paper describes for the first-time analytical procedures established to resolve the challenges associated with simultaneous and direct quantification of ataluren and ataluren-O-1 beta-acyl glucuronide (AAG) by LC-MS/MS in human plasma and urine matrices.Methodology/results:The plasma quantification method was validated for calibration range of 12.5-12500 ng/ml for ataluren and 6.25-2500 ng/ml for AAG. The urine quantification method was validated for calibration range of 0.01-10 and 1-1000 mu g/ml for ataluren and AAG, respectively. Plasma and urine samples were stabilized upon collection and through storage to prevent hydrolysis and acyl migration of AAG.Conclusion:Methods described in this paper enabled successful completion of ataluren clinical pharmacology studies for simultaneous pharmacokinetic assessment of ataluren and AAG.

引用

页码：1545 / 1555

页数：11

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