Quantitative analysis of clindamycin in human plasma by liquid chromatography/electrospray ionisation tandem mass spectrometry using d1-N-ethylclindamycin as internal standard

A new method for the quantitative analysis of clindamycin in human plasma by liquid chromatography/electrospray ionisation tandem mass spectrometry (LC/ESI-MS/MS) is presented. Recently published methods possess a disadvantage because of their use of internal standards with extraction and ionisation properties different from those of clindamycin. To avoid these problems, d(1)-N-ethylclindamycin was synthesised for use as internal standard by N-demethylation and subsequent d(1)-N-ethylation. Plasma sample preparation was done by an easy and rapid liquid-liquid extraction using ethyl acetate. The method was validated in the expected concentration range for a pharmacokinetic study. Calibration graphs were linear within the range 0.05-3.2 microg/mL plasma. Intra-day precision was between 0.90% (2.8 microg/mL) and 3.25% (0.05 microg/mL), inter-day variability was found to be between 1.33% (0.7 microg/mL) and 2.60% (0.05 microg/mL). Inter-day accuracy showed deviations between 0.4% (0.05 microg/mL) and -4.8% (0.2 microg/mL). The method is simple and robust, and has been applied to the batch analysis of clindamycin during a pharmacokinetic study.