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Validation of a liquid chromatography/tandem mass spectrometry method for the simultaneous quantification of Sotrastaurin and its metabolite N-desmethyl-sotrastaurin in human blood

Jakab, Annamaria and Winter, Serge and Guy, Bertrand and Raccuglia, Marc and Picard, Franck and Kovarik, John M. and Chudasama, Jayraj and Guttikar, Swati and Singhal, Puran and Kretz, Olivier (2012) Validation of a liquid chromatography/tandem mass spectrometry method for the simultaneous quantification of Sotrastaurin and its metabolite N-desmethyl-sotrastaurin in human blood. Journal of Chromatography B, 897. pp. 10-16. ISSN 1570-0232

Abstract

A liquid chromatography/tandem mass spectrometry (HPLC–MS/MS) method was developed and validated for the quantification of Sotrastaurin (AEB071) and N-desmethyl-sotrastaurin (AEE800) in human blood. The validation of the analytical procedure was assessed according to the latest Food and Drug Administration “Guidance for Industry, Bioanalytical Method Validation”. Chromatographic separation was performed using an RP C18 column at 40±3.0 oC with a mobile phase consisted of 2mM ammonium acetate in water (pH 4.5): methanol: acetonitrile (25:15:60 v/v) of a flow rate of 1 mL/min followed by quantification with mass spectrometer, operated in electrospray ionization (ESI) positive ion mode and applying multiple reaction monitoring (MRM). The LC–MS/MS method described in this paper presents high absolute recovery (the overall mean recovery of Sotrastaurin and N-desmethly-sotrastaurin was 115.9% and 110.4% respectively), with a sensitivity of 3.00 ng/mL as lower limit of quantitation using a sample volume of 300 µL, low inter-day bias and precision (for Sotrastaurin, 0.4 to -4.4% and 1.8 to 5.2% and for N-desmethyl-sotrastaurin, ranged from 2.3 to -1.6% and 3.9 to 2.7%, respectively), with a short runtime of 3.5 min. The method was validated using K3EDTA as specific anticoagulant and cross-validated using Li-Heparin and Na-Heparin. The method was specific for Sotrastaurin and N-desmethly-sotrastaurin within the given criteria of acceptance (apparent peak area for Sotrastaurin and N-desmethly-sotrastaurin in zero samples ≤ 20% of mean peak area at LLOQ) in human blood. The method was fully validated for the quantitative determination of Sotrastaurin and its metabolite N-desmethyl-sotrastaurin in human blood between the range of 3 ng/mL and 1200 ng/mL.

Item Type: Article
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Additional Information: The article will be submitted by the publishing group in India once the OAK process has been finished
Keywords: Sotrastaurin, N-desmethyl-sotrastaurin, AEB071, AEE800, Metabolite, LC-MS/MS, Stability, Human blood, Recovery, Validation
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Date Deposited: 13 Oct 2015 13:14
Last Modified: 13 Oct 2015 13:14
URI: https://oak.novartis.com/id/eprint/5913

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