高效液相色谱-质谱/质谱联用法测定人血浆中莫沙必利

建立测定人血浆中莫沙必利的高效液相色谱-质谱/质谱联用法。取血浆样品经液-液萃取后，以乙腈为有机相，0.3%甲酸水溶液为水相，采用梯度洗脱的方式，用C₁₈柱分离，通过电喷雾离子化，以多反应监测(MRM)方式进行正离子检测。莫沙必利线性范围为0.17~68.00 ng·mL^-1，定量下限为0.17 ng·mL^-1，每个样品测试时间仅2.8 min，日内、日间精密度(RSD)均小于13%，准确度(RE)在±6.3%范围内。应用此法研究了20名志愿者单剂量口服枸橼酸莫沙必利片后的药代动力学特点。该方法、灵敏、准确、快速，适用于莫沙必利的药代动力学及生物等效性研究。

Determination of mosapride in human plasma by high performance liquid chromatography tandem mass spectrometry

To develop a sensitive and specific high performance liquid chromatography-tandem mass spectrometric (HPLC-MS/MS) method for the determination of mosapride in human plasma, mosapride and internal standard tamsulosin were extracted from plasma with liquid-liquid extraction, then separated on a Waters ACQUITY UPLC BEH C18 column (50 mm x 2.1 mm, 1.7 microm ID) with gradient elution at flow-rate of 0.25 mL x min(-1). The mobile phase was water (containing 0.3% formic acid) and acetonitrile under gradient conditions. Electrospray ionization (ESI) source was applied and operated in the positive ion mode. Multiple reaction monitoring (MRM) mode with the transitions of m/z 422 --> m/z 198 and m/z 409 --> m/z 228 were used to quantify mosapride and the internal standard, respectively. The linear calibration curve was obtained in the concentration range of 0.17 - 68.00 ng x mL(-1). The lower limit of quantification was 0.17 ng x mL(-1). The inter- and intra-day precision (RSD) was less than 13%, and the accuracy (RE) was within +/- 6.3% calculated from QC samples. The method was used to determine the concentration of mosapride in plasma after a single oral dose of 5 mg mosapride citrate to 20 healthy male Chinese volunteers. The method has been proved to be selective, sensitive, rapid and suitable for pharmacokinetic study of mosapride.