Determination of Ganciclovir and its prodrug Valganciclovir by hydrophilic interaction liquid chromatography-tandem mass spectrometry

被引:29
作者
Heinig, Katja [1 ]
Wirz, Thomas [1 ]
Gajate-Perez, Almudena [1 ]
Belli, Sara [1 ]
机构
[1] F Hoffmann La Roche & Co Ltd, Pharma Res, Nonclin Safety, Bioanalyt Sect, CH-4070 Basel, Switzerland
来源
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES | 2011年 / 879卷 / 5-6期
关键词
Ganciclovir (GCV); Valganciclovir (VGC); Valcyte (R); Plasma; Liquid chromatography-tandem mass spectrometry (LC-MS/MS); Hydrophilic interaction liquid chromatography (HILIC); Dried blood spots (DBS); HUMAN PLASMA; HPLC METHOD; PHARMACOKINETICS; METABOLITE;
D O I
10.1016/j.jchromb.2010.12.033
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
This manuscript describes the determination of Ganciclovir (GCV), active component of the antiviral drug Valcyte(R), and its ester prodrug Valganciclovir (VGC) in human and rat plasma, using liquid chromatography coupled to tandem mass spectrometry. Protein precipitation with acetonitrile was followed by hydrophilic interaction liquid chromatography on a silica column with 4 min run time. After electrospray ionization, the compounds were detected in positive ion selected reaction monitoring (SRM) mode. The lower limits of quantification (LLOQ) were 16 ng/mL for GCV and 4 ng/mL for VGC in human and rat plasma. Inter-day and intra-day precisions and inaccuracies were below 15% and between 85 and 115%, respectively. Five-fold deuterated GCV and VGC were used as internal standards and compensated for any matrix effect. The method was successfully applied to samples from a rat pharmacokinetic study. The feasibility of blood analysis as dried blood spots (DBS) was investigated. (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码:436 / 442
页数:7
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