Determination of propranolol in rat plasma by HPLC-MS/MS and its application in pharmacokinetic study

OBJECTIVE To establish an HPLC-MS/MS method to determine the content of propranolol in rat plasma, and to study the pharmacokinetic characteristics of propranolol in rats after oral administration. METHODS The plasma samples were treated with methanol precipitation protein method. LC-MS/MS method was developed and validated for the determination of propranolol in rats using mexiletin as the internal standard. ZORBAX Eclipse Plus C₁₈column (2.1 mm×100 mm, 3.5 μm) was used, the mobile phase consisting of water containing 0.1% formic acid and acetonitrile (70:30). The detection parameters of mass spectrometry were as follows:ESI ionization source, positive polarity. Ions monitored in the multiple reaction monitoring (MRM) mode were m/z 260.2→116.2 for propranolol and m/z 180.2→58.2 for mexiletin (internal standard). RESULTS Calibration curves were linear in range of 5-1 000 ng∙mL^-1 for propranolol. Intra-and inter-day precision and accuracy were 0.36%-6.39% and 96.19%-113.38%, respectively. Extraction recovery ranged 86.82%-96.12%, and the matrix effect of propranolol ranged 100.1%-103.1%. CONCLUSION The LC-MS/MS method is accurate and sensitive, and is successfully applied to evaluate the pharmacokinetics of propranolol in rats plasma.