Validation and reproducibility of an LC-MS/MS method for emixustat and its three deaminated metabolites in human plasma

被引：2
|
作者：
Podoll, Terry [1 ]
Geisler, Lisa [2 ]
Van Parys, Michael [2 ]
Hanson, Glenn [2 ]
Reid, Michael J. [3 ]
机构：
[1] IV PO LLC, 5021 Bowen Pl South, Seattle, WA 98118 USA
[2] Covance Labs Inc, 3301 Kinsman Blvd, Madison, WI 53704 USA
[3] Acucela Inc, 21720 23rd Dr SE,Suite 120, Bothell, WA 98021 USA
来源：
BIOANALYSIS | 2018年 / 10卷 / 22期
关键词：
emixustat; incurred sample reanalysis (ISR); major metabolite; metabolites in safety testing (MIST); oxidative deamination; visual cycle; HYDROCHLORIDE; ACU-4429; SAFETY;
D O I：
10.4155/bio-2018-0159
中图分类号：
Q5 [生物化学];
学科分类号：
071010 ; 081704 ;
摘要：
Aim: A sensitive method to quantify emixustat and its rapidly formed three major deaminated metabolites in human plasma was necessary to determine exposure in clinical trials. Methods: An LC-MS/MS method was validated for accuracy and precision, linearity, carry over, selectivity, recovery, matrix effects, hematocrit effects and stability. Results: A quantitative procedure for the determination of emixustat, ACU5116, ACU-5124 and ACU-5149 in human plasma over the concentration range of 0.0500/1.00/1.00/1.0010.0/1000/1000/1000 ng/ml, was successfully validated and has been used to successfully analyze samples in three clinical trials. Incurred sample reanalysis was performed for all four analytes in each study with >92% of the repeat results and original results within 20% of the mean of the two values.
引用
收藏
页码：1803 / 1817
页数：15
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