运用高效液相色谱-串联质谱联用技术，建立了简单、快速、灵敏的比格犬灌胃莫诺苷后血药浓度的检测方法。血浆样品采用蛋白质沉淀法处理，以芍药苷作为内标，色谱柱为 Inertsil ODS-SP 色谱柱（50 mm ×2.1 mm，5μm），流动相为水（含1 mmol / L 甲酸钠）-乙腈，梯度洗脱，流速0.4 mL / min。采用电喷雾离子源（ ESI），正离子多反应监测（MRM）模式。绘制血药浓度-时间曲线，并采用 DAS 2.0软件计算药代动力学参数。方法学实验结果表明内源性杂质不干扰莫诺苷和内标的测定，线性范围为2~5000μg / L（ r =0.9966），定量限为2μg / L。方法精密度、准确度、回收率和基质效应均符合生物样品测定的要求，适合比格犬血浆中莫诺苷浓度的测定，可以应用该方法进行莫诺苷的药代动力学研究。比格犬灌胃莫诺苷3个剂量（5、15、45 mg / kg）后的血药浓度-时间曲线下面积（AUC（0-∞））分别为（1631.20±238.50）、（3984.05±750.38）、（10397.64±3156.34）μg / L·h，与给药剂量之间呈现良好的线性关系。
A sensitive,simple and specific high performance liquid chromatography-electros-pray ionization tandem mass spectrometry( LC-MS / MS)method was developed for the deter-mination of morroniside in the plasma of beagles administered via intragastric( ig)doses of morroniside. The method employed paeoniflorin as the internal standard and extracted by sim-ple protein precipitation. The separation was achieved using an Inertsil ODS-SP column(50 mm ×2. 1 mm,5 μm)with mobile phases of 1 mmol / L sodium formate aqueous solution and aceto-nitrile(gradient elution)at a flow rate of 0. 4 mL / min. The detection was accomplished by a mass spectrometer using multiple reaction monitoring( MRM)in positive mode. Pharmacoki-netic parameters were fitted by software DAS 2. 0. The methodological study showed a good lin-ear relationship of 2-5 000 μg / L(r = 0. 996 6)with a sensitivity of 2 μg / L as the limit of quanti-fication. The precision,accuracy,mean recoveries and the matrix effects were satisfied with the requirements of biological sample measurement. The method described above was success-fully applied to the pharmacokinetic study of morroniside in the beagle plasma samples. The area under the plasma concentration-time curves( AUC( 0-∞ )) of morroniside after single ig administration doses of 5,15 and 45 mg / kg were(1 631. 20±238. 50),(3 984. 05±750. 38)and (10 397. 64±3 156. 34)μg / L·h. The relationship between dose and AUC showed a good linearity. The pharmacokinetic property of morroniside was proposed to be linear pharmacokinetics.
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