LC-MS determination of triazolam and its hydroxy metabolites in mouse dried blood spots: application to transgenic mouse pharmacokinetic studies

被引：8
|
作者：
Kole, Prashant [1 ]
Rao, Abhijith [1 ]
Kurawattimath, Vishwanath [1 ]
Mandlekar, Sandhya [1 ]
机构：
[1] Syngene Int Ltd, Biocon Bristol Myers Squibb R&D Ctr, Dept Pharmaceut Candidate Optimizat, Bangalore 560099, Karnataka, India
来源：
BIOANALYSIS | 2017年 / 9卷 / 13期
关键词：
dried blood spot; drug-drug interaction; LC-MS/MS; metabolites; method validation; pharmacokinetic study; surrogate biomatrix; triazolam; TANDEM MASS-SPECTROMETRY; PHASE LIQUID-CHROMATOGRAPHY; HUMAN LIVER-MICROSOMES; ALPHA-HYDROXYTRIAZOLAM; QUANTITATIVE BIOANALYSIS; HUMAN PLASMA; BENZODIAZEPINES; HEMATOCRIT; MS/MS; HAIR;
D O I：
10.4155/bio-2017-0067
中图分类号：
Q5 [生物化学];
学科分类号：
071010 ; 081704 ;
摘要：
The objective of this study was to develop a LC-MS/MS method for the simultaneous determination of triazolam (TRZ) and its two hydroxy metabolites in transgenic mouse dried blood spots ( DBS) using BALB/c mouse blood as a surrogate biomatrix. Methodology/Results: The DBS method involved spotting volume of 10 ae l using Ahlstrom 226 sample collection cards. A 'whole spot' analysis (6-mm punch) involved extraction of analytes using water and acetonitrile containing an internal standard. DBS samples were analyzed by a validated LC-MS/MS method with a run time of 4 min. Conclusion: This validated LC-MS/MS method using DBS extraction was applied to quantitation of TRZ, alpha-hydroxytriazolam and 4-hydroxytriazolam in a CYP3A4 transgenic mouse oral pharmacokinetic study of TRZ.
引用
收藏
页码：987 / 1000
页数：14
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