title: 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.
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 C(18) 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.
authors.affiliation: Incozen Therapeutics Pvt. Ltd, Alexandria Knowledge Park, Shamirpet, Hyderabad, 500078, India.
authors.forename: Satheeshmanikandan R S
authors.initials: SR
authors.lastname: Thappali
authors.forename: Kanthikiran
authors.initials: K
authors.lastname: Varanasi
authors.forename: Sridhar
authors.initials: S
authors.lastname: Veeraraghavan
authors.forename: Rambabu
authors.initials: R
authors.lastname: Arla
authors.forename: Sandhya
authors.initials: S
authors.lastname: Chennupati
authors.forename: Madheswaran
authors.initials: M
authors.lastname: Rajamanickam
authors.forename: Swaroop
authors.initials: S
authors.lastname: Vakkalanka
authors.forename: Mukkanti
authors.initials: M
authors.lastname: Khagga