Quantification of isoniazid and acetylisoniazid in rat plasma and alveolar macrophages by liquid chromatography-tandem mass spectrometry with on-line extraction

被引：19
作者：
Ng, Ka-yun
Zhou, Huiyu
Zhang, Yan Ling
Hybertson, Brooks
Randolph, Theodore
Christians, Uwe
机构：
[1] Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Denver, CO 80262 USA
[2] Univ Colorado, Hlth Sci Ctr, Dept Anesthesiol, Clin Res & Dev, Denver, CO 80262 USA
[3] Univ Colorado, Hlth Sci Ctr, Webb Waring Inst Canc Aging & Antioxidant Res, Denver, CO 80262 USA
[4] Univ Colorado, Hlth Sci Ctr, Sch Med, Denver, CO 80262 USA
[5] Univ Colorado, Ctr Pharmaceut Biotechnol, Dept Chem & Biol Engn, Boulder, CO 80309 USA
来源：
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES | 2007年 / 847卷 / 02期
关键词：
acetylated isoniazid; isoniazid; LC/LC-MS/MS; microparticles; PLA; pharmacokinetics; tuberculosis;
D O I：
10.1016/j.jchromb.2006.10.008
中图分类号：
Q5 [生物化学];
学科分类号：
071010 ; 081704 ;
摘要：
To evaluate if pulmonary delivery of microparticles loaded with a prodrug of isoniazid (INH), isoniazid methanesulfonate (INHMS), can target alveolar macrophages (AM) and reduce metabolism of INH, an HPLC-MS/MS assay with automated online extraction for quantification of INH and its metabolite acetylisoniazid (AcINH) in plasma and AMs was developed and validated. Reproducibility in rat plasma and homogenate of a rat AM cell line, NR8383, for INH and AcINH showed excellent precision and accurac, with calibration curves exhibiting linearity within a range y of 1-250ng/ml of INH and 0.05-50ng/ml of AcINH (r(2) > 0.99). The validated methods were successfully applied to pharmacokinetic study of INHMS-loaded microparticles in rats, demonstrating efficient targeting of AMs and reduction of INH metabolism. (c) 2006 Elsevier B.V. All rights reserved.
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收藏
页码：188 / 198
页数：11
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