Simultaneous estimation of paclitaxel and erlotinib in plasma by liquid chromatography/(+) electrospray tandem mass spectrometry: application in formulation development and pharmacokinetics.

ABSTRACT

The bio-analytical method was developed and validated for simultaneous detection and quantification of paclitaxel (PAC) and erlotinib (ERL) in plasma samples. The sample preparation process was accomplished by liquid-liquid extraction technique. The dried and reconstituted samples were subjected to chromatography on Discovery -C18 (50 × 4.6 × 5µm) column and a mobile phase, composed of a mixture of 0.1% formic acid in water acetonitrile (7030, v/v), in isocratic mode at a flow rate of 0.6 mL/min. Liquid chromatography coupled to tandem mass spectrometry detection in positive ion mode was selected to provide optimal selectivity and sensitivity. The mass transitions of erlotinib, erlotinib13C6, Paclitaxel and docetaxel were m/z 394.5→278.4, m/z 400.4→284.5, m/z 876.6→308.4 and m/z 830.0→304.0 respectively. The linearity in the calibration curves was obtained in the concentration range of 3.6 - 1006.7 ng/ml (r ≥ 0.99) for erlotinib and 5.3 - 1500.0 ng/mL for paclitaxel with an LLOQ (lower limit of quantification) of 3.6 and 5.3 ng/ml respectively. The run time was achieved in 2.5 min only, for all the analytes.