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目的建立测定大鼠血浆中间氯苯基哌嗪(m-chlorophenylpiperazine,m-CPP)的UPLC-MS/MS方法,并应用该法比较了按m-CPP计相同剂量下,大鼠灌胃给予盐酸WS和盐酸曲唑酮后,m-CPP在大鼠体内的药物动力学行为。方法色谱柱为Thermo Hypersi L GOLD a Q C18柱(100 mm×2.1mm,1.9μm),流动相为乙腈-体积分数0.1%甲酸水溶液梯度洗脱,采用乙腈沉淀蛋白法处理血浆样品,以正离子扫描多反应监测模式进行检测。结果大鼠血浆中的m-CPP在质量浓度为0.20~152.10μg·L-1内线性关系良好(r=0.998 4),定量下限为0.20μg·L-1,提取回收率大于85%,日内和日间精密度均小于7%,准确度为100.8%~103.5%。20只Sprague Dawley大鼠分别灌胃给予盐酸曲唑酮9.9 mg·kg-1(按m-CPP计4.8 mg·kg-1)和盐酸WS 10.2 mg·kg-1(按m-CPP计4.8mg·kg-1)生理盐水溶液,血浆中m-CPP的tmax分别为(0.6±0.3)和(0.6±0.2)h,ρmax分别为(32.6±16.2)和(22.3±12.0)μg·L-1,AUC0-10分别为(89.0±27.5)和(66.3±17.1)μg·h·L-1,AUC0-∞分别为(96.8±26.8)和(75.3±15.5)μg·h·L-1,t1/2分别为(3.1±1.6)和(4.0±3.9)h。结论盐酸WS组中m-CPP的AUC0-10和AUC0-∞均大于盐酸曲唑酮组(P<0.05),Cl小于盐酸曲唑酮组(P<0.05),其他药动学参数无显著性差异(P>0.05)。
Objective To establish an UPLC-MS / MS method for the determination of m-chloropiperazine (m-CPP) in rat plasma and to compare the effects of hydrochloric acid Pharmacokinetics of m-CPP in rats after WS and trazodone hydrochloride. Methods The column was a Thermo Hypersi L GOLD a Q C18 column (100 mm × 2.1 mm, 1.9 μm). The mobile phase consisted of a gradient elution of acetonitrile and 0.1% formic acid in water. The plasma samples were treated with acetonitrile precipitation protein, Scan multiple reaction monitoring mode for detection. Results The linearity of m-CPP in plasma was 0.20 ~ 152.10 μg · L-1 (r = 0.998 4), the lower limit of quantitation was 0.20 μg · L-1 and the recovery of m-CPP was more than 85% And daytime precision less than 7%, accuracy of 100.8% ~ 103.5%. Twenty Sprague Dawley rats were orally administered with trazodone hydrochloride at 9.9 mg · kg -1 (4.8 mg · kg -1 by m-CPP) and WS 10.2 mg · kg -1 HCl (4.8 mg m-CPP · Kg-1), the tmax of plasma m-CPP were (0.6 ± 0.3) and (0.6 ± 0.2) h respectively and the ρmax were (32.6 ± 16.2) and (22.3 ± 12.0) μg · L -1 AUC0-10 were (89.0 ± 27.5) and (66.3 ± 17.1) μg · h · L-1, respectively, and AUC0-∞ were (96.8 ± 26.8) and (75.3 ± 15.5) μg · h · L- / 2 were (3.1 ± 1.6) and (4.0 ± 3.9) h, respectively. CONCLUSION: AUC0-10 and AUC0-∞ of m-CPP in hydrochloric acid WS group are greater than that of trazodone hydrochloride group (P <0.05), Cl is less than that of trazodone hydrochloride group (P <0.05), and other pharmacokinetic parameters are not significant Difference (P> 0.05).