Quantitative determination of rosuvastatin in human plasma by ion pair liquid-liquid extraction using liquid chromatography with electrospray ionization tandem mass spectrometry.

Abstract A simple and sensitive liquid chromatography/tandem mass spectrometry method was developed and validated for the quantification of rosuvastatin in human plasma. After being treated with acetic acid and tetrabutyl ammonium hydroxide, the analyte was extracted by simple one-step liquid–liquid extraction with the internal standard (IS: estrone). The chromatographic separation was performed on a Phenomenex Luna C 18 column with a mobile phase consisting of 2% formic acid/methanol (20:90, v/v) at a flow rate of 1.00 mL/min with a split of 200 μL to mass spectrometer. The retention time of rosuvastatin and internal standard was 2.3 and 3.4 min, respectively. Triple–quadrupole MS/MS detection was operated in positive mode by monitoring the transition of m / z 482 → 258 for rosuvastatin and m / z 271 → 253 for IS. Validation results indicated that the lower limit of quantification (LLOQ) was 0.1 ng mL −1 and the assay exhibited a linear range of 0.1–20 ng mL −1 and gave a correlation coefficient ( r ) of 0.9990 or better. Inaccuracy was less than 8.4% and imprecision less than 12.8% at all tested concentration levels. The analyte was stable in human plasma following three freeze/thaw cycles and for up to 8 weeks following storage at −20 °C. The assay was successfully applied to the analysis of rosuvastatin in human plasma samples derived from clinical pre-trials.