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J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Mar 1;951-952:62-8. doi: 10.1016/j.jchromb.2014.01.017. Epub 2014 Jan 19.

Development and validation of a sensitive LC-MS/MS method for simultaneous quantification of sinotecan and its active metabolite in human blood.

Author information

  • 1Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China; Department of Clinical Pharmacy, Bethune International Peace Hospital, 398 West Zhongshan Road, Shijiazhuang 050082, PR China.
  • 2Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China.
  • 3Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China. Electronic address: dfzhong@mail.shcnc.ac.cn.

Abstract

Sinotecan is a camptothecin analog, currently under clinical testing as an antitumor medication. We developed and validated a rapid, specific and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of sinotecan and its active metabolite, 7-hydroxyethyl-camptothecin (7-HEC), in human blood. Aliquots (200μL) of heparinized blood samples were processed by deproteinization with 400μL acetonitrile each. Chromatographic analyte separation used an Agilent Zorbax SB C8 column (4.6mm×150mm, 5μm) and methanol/10mM ammonium acetate/formic acid (70/30/0.14, v/v/v) as mobile phase, at a flow rate of 0.60mL/min. A Thermo Finnigan TSQ Quantum Ultra tandem mass spectrometer was operated in multiple-reaction monitoring mode. The precursor-to-product ion transitions m/z 493→m/z (331+375) for sinotecan, m/z 393→m/z (233+261) for 7-HEC, and m/z 396→m/z 352 for d3-SN38 (IS) were used for quantification. The method was validated for 1.0-500ng/mL for sinotecan and 0.5-250ng/mL for 7-HEC using 200μL of blood sample. Total time for each chromatograph was ∼6.0min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD)<13.8% and the accuracy values ranged from -5.3% to 2.4%. The method was successfully applied to a pharmacokinetic study of sinotecan in cancer patients.

Copyright © 2014 Elsevier B.V. All rights reserved.

KEYWORDS:

7-Hydroxyethyl-camptothecin; LC-MS/MS; Pharmacokinetics; Sinotecan

PMID:
24534567
[PubMed - in process]
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