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

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 (150 mm × 4 mm i.d., 5 μm) column using mixture of methanol: acetonitrile: 2 mM ammonium acetate (25:25:50, v/v, pH 3.5) at 0.8 mL/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, 0.04–4.4 μg/mL and 0.1–10.0 μg/mL for CDPX and CA respectively. Pharmacokinetic parameters of tablet (CDPX 200 mg, CA 125 mg) were evaluated. Cmax, Tmax, T1/2, elimination rate constant (Kel), AUC0–t, and AUC0–∞ of tablet were 2.13 ± 0.06 μg/mL, 2 h, 3.05 ± 0.15 h, 0.24 ± 0.37 h−1, 6.81 ± 0.14 μg h/mL and 7.72 ± 0.23 μg h/mL respectively for cefpodoxime (CP), 5.34 ± 0.28 μg/mL, 2 h, 2.73 ± 0.25 h, 0.26 ± 0.31 h−1, 15.37 ± 0.16 μg h/mL and 16.59 ± 0.53 μg h/mL respectively for CA.

► There was no LC–MS method reported for the simultaneous determination of CP and CA in biological samples. ► We developed and validated a rapid and sensitive LC–MS method for simultaneous estimation of CP and CA in human plasma. ► We evaluated the pharmacokinetic variables of tablet (containing CP 200 mg and CA 125 mg) after a single oral dose administration in twelve healthy human volunteers.