A validated UPLC-MS/MS method to determine free and total irinotecan and its two metabolites in human plasma after intravenous administration of irinotecan hydrochloride liposome injection

Publication date: Available online 18 March 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Quankun Zhuang, Xuemei Liu, Zhuo Sun, Hongyun Wang, Ji JiangAbstractIrinotecan hydrochloride liposome injection (IHLI) is a formulation of anticancer drug irinotecan hydrochloride (CPT-11) entrapped in the aqueous core of liposomes. To understand the pharmacokinetic property and evaluate the relationship between pharmacokinetics and pharmacodynamics/toxicity of IHLI, it is of prime importance to determine the concentrations of free CPT-11, total CPT-11 and its main metabolites (SN-38 and SN-38 G) in human plasma. In this paper, we developed and validated a sensitive and reliable ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to quantify the concentrations of these related substances in human plasma. Free CPT-11, SN-38 and SN-38 G in human plasma were simultaneously separated and extracted by 96-well solid phase extraction (SPE) plate, while total CPT-11 was extracted by protein precipitation (PP) method. The analytes were chromatographed on an Acquity UPLC BEH C18 column and then detected on a Xevo TQ-S tandem mass spectrometer in multiple reactions monitoring (MRM) mode using positive electrospray ionization (ESI). The UPLC-MS/MS method combined with SPE and PP techniques were fully validated in line with existing guidelines issued by regulatory agencies. In brief, all the analytes achieved a satisfactory selectivity an...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research