title: Bioanalysis of drug in tissue: current status and challenges.
abstract: Distribution of drugs into tissues is an important determinant of the overall PK and PD profile. Thus, bioanalysis of drugs and their metabolites in tissues can play an important role in understanding the pharmacological and toxicological properties of new drug candidates. Unlike liquid matrices, bioanalysis in tissues offers unique challenges such as proper tissue sampling, appropriate tissue sample preparation, efficient extraction of the analytes from the tissue homogenates, and demonstration of stability and recovery of analytes in intact tissues. This article provides a systematic review of tissue sample analysis for small molecules using LC-MS/MS. The authors provide rationale for tissue sample analysis, and discuss strategies for method development, method qualification or validation, and sample analysis. Unique aspects of method development and qualification/validation are highlighted based on authors' direct experiences and literature summary. Analysis using intact tissue samples such as MALDI imaging is also briefly discussed.
authors.affiliation: Celgene Corporation, Summit, NJ 07901, USA. yoxue@celgene.com
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Xue
authors.forename: Hong
authors.initials: H
authors.lastname: Gao
authors.forename: Qin C
authors.initials: QC
authors.lastname: Ji
authors.forename: Zamas
authors.initials: Z
authors.lastname: Lam
authors.forename: Xinping
authors.initials: X
authors.lastname: Fang
authors.forename: Zhongping John
authors.initials: ZJ
authors.lastname: Lin
authors.forename: Matthew
authors.initials: M
authors.lastname: Hoffman
authors.forename: Daniel
authors.initials: D
authors.lastname: Schulz-Jander
authors.forename: Naidong
authors.initials: N
authors.lastname: Weng
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D013058:Mass Spectrometry; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000378:metabolism; D013048:Specimen Handling; D016707:Tissue Fixation
chemical_list: D004364:Pharmaceutical Preparations