Quantitation of Solifenacin in Human Plasma Using a Specific and Sensitive Liquid Chromatography-Tandem Mass Spectrometry Technique

Abstract

Purpose: The current work validated a high performance liquid chromatography-tandem mass spectrometric (HPLC-MS/MS) bioassay method developed in-house for the quantitation of solifenacin in human plasma. Methods: Solifenacin was extracted from plasma by a liquid-liquid extraction (LLE) technique using tertbutyl methyl ether. The dry extract was then reconstituted with 200 μL of the mobile phase (acetonitrilewater (80:20, v/v)). Solifenacin-d5 was the internal standard (IS). Elution was carried out on a C18 column at a flow rate of 1 mL/min. The MS/MS employed turbo-ion spray ionization in the positive ion mode. Solifenacin and IS were monitored at a mass to charge ratio (m/z) of 363.4 and 368.4, respectively. Bioassay validation followed International Bioanalytical Method Validation Guidelines. Results: The validated calibration curves were linear over a range of 0.5 – 60.0 ng/mL (regression factors ≥ 0.9994). Method specificity was established in 6 different human plasma batches. Intra- and inter-day precision and accuracy were within ± 20% (for lower limit of quantitation (LLOQ)) and ± 15% (for low, mid and high quality control (QC) levels). Short- and long-term stability was within accepted range. Conclusion: A specific, accurate and precise HPLC-MS/MS method has been validated for the determination of solifenacin in human plasma.