Determination of Cefotiam in Human Plasma Using Liquid Chromatography-Tandem Mass Spectrometry

In order to evaluate the pharmacokinetic profile of cefotiam hexetil hydrochloride tablet in Chinese healthy volunteers, a sensitive, specific and rapid "protein precipitation. liquid chromatography. tandem mass spectrometry" method was developed and validated in human plasma. Chromatographic separation was achieved on a Waters Symmtry-C-18 column (50 mm x 4.6 mm, 5 mu m), using a gradient mobile phase consisting of methanol and 1 mmol/L ammonium acetate in water at a flow rate of 1.0 mL/min. Cefotiam and diazepam (internal standard) were detected without interference in the multiple reaction monitoring (MRM) mode with positive electrospray ionization. The calibration curve was linear from 5.0 ng/mL to 5000 ng/mL (r>0.99) with limit of quantitation of 5.0 ng/mL. The assay met the published acceptance criteria. This rapid, sensitive and reproducible method was successfully applied to the pharmacokinetic study of cefotiam hexetil hydrochloride tablet in healthy Chinese volunteers and therefore provided a considerable mirror for quantification of other cephalosporins in human matrix.