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Sci. Pharm. 2012, 80(3), 633-646; doi:10.3797/scipharm.1205-09

Simultaneous Determination of Celecoxib, Erlotinib, and its Metabolite Desmethyl-Erlotinib (OSI-420) in Rat Plasma by Liquid chromatography/Tandem Mass Spectrometry with Positive/Negative Ion-Switching Electrospray Ionisation

1
Incozen Therapeutics Pvt. Ltd, Alexandria Knowledge Park, Shamirpet, Hyderabad, 500078, India
2
Centre for Pharmaceutical Sciences, JNT University, Kukatpally, Hyderabad, India
*
Author to whom correspondence should be addressed.
Received: 17 May 2012 / Accepted: 18 June 2012 / Published: 18 June 2012
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Abstract

A new method for the simultaneous determination of celecoxib, erlotinib, and its active metabolite desmethyl-erlotinib (OSI-420) in rat plasma, by liquid chromatography/tandem mass spectrometry with positive/negative ion-switching electrospray ionization mode, was developed and validated. Protein precipitation with methanol was selected as the method for preparing the samples. The analytes were separated on a reverse-phase C18 column (50mm×4.6mm i.d., 3μ) using methanol: 2 mM ammonium acetate buffer, and pH 4.0 as the mobile phase at a flow rate 0.8 mL/min. Sitagliptin and Efervirenz were used as the internal standards for quantification. The determination was carried out on a Theremo Finnigan Quantam ultra triple-quadrupole mass spectrometer, operated in selected reaction monitoring (SRM) mode using the following transitions monitored simultaneously: positive m/z 394.5→278.1 for erlotinib, m/z 380.3→278.1 for desmethyl erlotinib (OSI-420), and negative m/z −380.1→−316.3 for celecoxib. The limits of quantification (LOQs) were 1.5 ng/mL for Celecoxib, erlotinib, and OSI-420. Within- and between-day accuracy and precision of the validated method were within the acceptable limits of < 15% at all concentrations. The quantitation method was successfully applied for the simultaneous estimation of celecoxib, erlotinib, and desmethyl erlotinib in a pharmacokinetic study in Wistar rats.
Keywords: Celecoxib; Erlotinib; Desmethyl erlotinib; OSI-420; LC-MS/MS; Bioanalytical Celecoxib; Erlotinib; Desmethyl erlotinib; OSI-420; LC-MS/MS; Bioanalytical
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

THAPPALI, S.R.S.; VARANASI, K.; VEERARAGHAVAN, S.; ARLA, R.; CHENNUPATI, S.; RAJAMANICKAM, M.; VAKKALANKA, S.; KHAGGA, M. Simultaneous Determination of Celecoxib, Erlotinib, and its Metabolite Desmethyl-Erlotinib (OSI-420) in Rat Plasma by Liquid chromatography/Tandem Mass Spectrometry with Positive/Negative Ion-Switching Electrospray Ionisation. Sci. Pharm. 2012, 80, 633-646.

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