Simultaneous determination of etoposide and a piperine analogue (PA-1) by UPLC 13qTOF-MS: Evidence that PA-1 enhances the oral bioavailability of etoposide in mice

Sachin, B.S. and Najar, I.A. and Sharma, S.C. and Verma, M.K. and Reddy, M.V. and Anand, R. and Khajuria, R.K. and Koul, S. and Johri, R.K. (2010) Simultaneous determination of etoposide and a piperine analogue (PA-1) by UPLC 13qTOF-MS: Evidence that PA-1 enhances the oral bioavailability of etoposide in mice. Journal of Chromatography B, 878 (9-10). pp. 823-830. ISSN 15700232

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Official URL: http://dx.doi.org/10.1016/j.jchromb.2010.01.048

Abstract

In the present investigation, a UPLC-qTOF-MS/MS method has been developed for the simultaneous determination of etoposide and a piperine analogue, namely, 4-ethyl 5-(3,4-methylenedioxyphenyl)-2E,4E-pentadienoic acid piperidide (PA-1). The analytes were separated on a reverse phase C18 column using methanol-water (72:28, v/v) mobile phase with a flow rate of 250 microL/min. The qTOF-MS was operated under multiple reaction monitoring mode using electro-spray ionization (ESI) technique with positive ion polarity. The major product ions for etoposide and PA-1 were at m/z 185.1350 and 164.1581, respectively. The recovery of the analytes from mouse plasma was optimized using solid phase extraction technique. The total run time was 6 min and the elution of etoposide and PA-1 occurred at 1.24 and 2.84 min, respectively. The calibration curves of etoposide as well as PA-1 were linear over the concentration range of 2-1000 ng/mL (r(2), 0.9829), and 1-1000 ng/mL (r(2), 0.9989), respectively. For etoposide intra-assay and inter-assay accuracy in terms of % bias was in between -7.65 to +6.26, and -7.83 to +5.99, respectively. For PA-1 intra-assay and inter-assay accuracy in terms of % bias was in between -7.01 to +9.10, and -7.36 to +6.71, respectively. The lower limit of quantitation for etoposide and PA-1 were 2.0 and 1.0 ng/mL, respectively. Analytes were stable under various conditions (in autosampler, during freeze-thaw, at room temperature, and under deep-freeze conditions). The method was used for a pharmacokinetic study which showed that PA-1 enhanced the oral bioavailability of etoposide in mice by 2.32-fold.

Item Type:	Article
Subjects:	Chemical Sciences
Divisions:	UNSPECIFIED
Depositing User:	Mr. Amit Nargotra
Date Deposited:	02 Jan 2012 12:14
Last Modified:	02 Jan 2012 12:14
URI:	http://iiim.csircentral.net/id/eprint/341

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