Simultaneous quantification of cefpodoxime proxetil and clavulanic acid in human plasma by LC–MS using solid phase extraction with application to pharmacokinetic studies

Abstract

A simple, rapid and selective high performance liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (HPLC-APCI-MS) method was developed and validated for the simultaneous estimation of cefpodoxime proxetil (CDPX) and clavulanic acid (CA) in human plasma. Extraction of samples was done by solid phase extraction technique (SPE) and chloramphenicol used as internal standard. Chromatographic separation was carried out on a reverse phase Princeton SPHER C18 (150mm×4mm i.d., 5μm) column using mixture of methanol: acetonitrile: 2mM ammonium acetate (25:25:50, v/v, pH 3.5) at 0.8mL/min flow rate. Detection was performed on a single quadrupole MS by selected ion monitoring (SIM) mode via APCI source. The calibration curve was linear within the concentration range, 0.04-4.4μg/mL and 0.1-10.0μg/mL for CDPX and CA respectively. Pharmacokinetic parameters of tablet (CDPX 200mg, CA 125mg) were evaluated. Cmax, Tmax, T1/2, elimination rate constant (Kel), AUC0-t, and AUC0-∞ of tablet were 2.13±0.06μg/mL, 2h, 3.05±0.15h, 0.24±0.37h(-1), 6.81±0.14μg h/mL and 7.72±0.23μg h/mL respectively for cefpodoxime (CP), 5.34±0.28μg/mL, 2h, 2.73±0.25h, 0.26±0.31h(-1), 15.37±0.16μg h/mL and 16.59±0.53μg h/mL respectively for CA.