Development and validation of a highly sensitive LC-MS/MS method for simultaneous quantitation of ethionamide and ethionamide sulfoxide in human plasma: application to a human pharmacokinetic study

A highly sensitive and specific LC‐MS/MS method has been developed for simultaneous quantification of ethionamide and ethionamide sulfoxide in human plasma (300 µL) using prothionamide as an internal standard (IS). Solid‐phase extraction was used to extract ethionamide, ethionamide sulfoxide and IS...

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Bibliographic Details
Published in:Biomedical chromatography 2011-09, Vol.25 (9), p.985-994
Main Authors: Deshpande, Abhijeet Y., Gurav, Sandip, Punde, Ravindra, Zambre, Vishal, Kulkarni, Rahul, Pandey, Sarvesh, Mungantiwar, Ashish, Mullangi, Ramesh
Format: Article
Language:English
Subjects:
Antitubercular Agents - blood
Antitubercular Agents - pharmacokinetics
Chromatography, Liquid - methods
Drug Stability
ethionamide
Ethionamide - blood
Ethionamide - pharmacokinetics
ethionamide sulfoxide
human plasma
Humans
LC-MS/MS
method validation
pharmacokinetics
Safrole - analogs & derivatives
Safrole - metabolism
Safrole - pharmacokinetics
Sensitivity and Specificity
Spectrometry, Mass, Electrospray Ionization - methods
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Summary:A highly sensitive and specific LC‐MS/MS method has been developed for simultaneous quantification of ethionamide and ethionamide sulfoxide in human plasma (300 µL) using prothionamide as an internal standard (IS). Solid‐phase extraction was used to extract ethionamide, ethionamide sulfoxide and IS from human plasma. The chromatographic separation of ethionamide, ethionamide sulfoxide and IS was achieved with a mobile phase consisting of 0.1% acetic acid : acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on a Peerless Basic C18 column. The total run time was 3.5 min and the elution of ethionamide, ethionamide sulfoxide and IS occurred at 2.50, 2.18 and 2.68 min, respectively. A linear response function was established for the range of concentrations 25.7–6120 ng/mL (r > 0.998) for ethionamide and 50.5–3030 ng/mL (r > 0.998) for ethionamide sulfoxide. The intra‐ and inter‐day precision values for ethionamide and ethionamide sulfoxide met the acceptance as per FDA guidelines. Ethionamide and ethionamide sulfoxide were stable in battery of stability studies, viz. bench‐top, autosampler and freeze–thaw cycles. The developed assay was applied to a pharmacokinetic study in humans. Copyright © 2011 John Wiley & Sons, Ltd.
ISSN:0269-3879
1099-0801
DOI:10.1002/bmc.1554