title: Quantification of isoniazid and acetylisoniazid in rat plasma and alveolar macrophages by liquid chromatography-tandem mass spectrometry with on-line extraction.
abstract: 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 accuracy with calibration curves exhibiting linearity within a range 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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, CO 80262, USA. phalnky@nus.edu.sg
authors.forename: Ka-yun
authors.initials: KY
authors.lastname: Ng
authors.forename: Huiyu
authors.initials: H
authors.lastname: Zhou
authors.forename: Yan Ling
authors.initials: YL
authors.lastname: Zhang
authors.forename: Brooks
authors.initials: B
authors.lastname: Hybertson
authors.forename: Theodore
authors.initials: T
authors.lastname: Randolph
authors.forename: Uwe
authors.initials: U
authors.lastname: Christians
mesh_terms: D000818:Animals; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D007538:Isoniazid / Q000031:analogs & derivatives* / Q000032:analysis* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D016676:Macrophages, Alveolar / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C510884:acetylisoniazid; D007538:Isoniazid