Determination of Sodium Tanshinone IIA Sulfonate in human plasma by LC–MS/MS and its application to a clinical pharmacokinetic study

• An LC–MS/MS method for the quantification of STS in human plasma is proposed.
• The pharmacokinetic profile of STS in human is reported.
• Sample preparation should be under yellow light to ensure the stability of the STS.

An assay based on protein precipitation and liquid chromatography–tandem mass spectrometry (LC–MS/MS) has been developed and validated for the quantitative analysis of Sodium Tanshinone IIA Sulfonate (STS) in human plasma. After the addition of dehydroepiandrosterone-D5-3-sulfate sodium salt (DHEAS-D5) as internal standard (IS) and formic acid, plasma samples were prepared by one-step protein precipitation with a mixture of acetonitrile and methanol. Isocratic mobile phase consisted of 0.4 mmol/L ammonium formate buffer (16 ppm formic acid)/acetonitrile (40/60, v/v) on a XSELECT™ HSS T3 column. Detection was performed on a triple-quadrupole mass spectrometer utilizing an electrospray ionization (ESI) interface operating in positive ion and selected reaction monitoring (SRM) mode with the precursor to product ion transitions m/z 373.3 → 357.1 for STS and m/z 373.0 → 97.8 for the IS. Calibration curves of STS in human plasma were linear (r = 0.9957–0.9998) over the concentration range of 2–1000 ng/mL with acceptable accuracy and precision. The lower limit of quantification in human plasma was 2 ng/mL. The validated LC–MS/MS method has been successfully applied to a pharmacokinetic study of STS in Chinese healthy male volunteers.