■米尔霉素肟(MBO)和吡喹酮(PZQ)具有广谱的生物活性,在兽医临床上常用于治疗寄生虫感染。在这项研究中,建立并验证了一种快速高效的LC-MS/MS法同时测定MBO,PZQ,顺式-4-羟基化-PZQ(C-4-OH-PZQ)和反式-4-羟基化-PZQ(T-4-OH-PZQ)和猫血浆中。
■通过乙腈蛋白沉淀从猫血浆中提取分析物和内标物,允许大批量样品的快速处理。MBO,PZQ,C-4-OH-PZQ,T-4-OH-PZQ,和内标(IS)在C18柱上用0.1%甲酸水/乙腈混合物作为流动相洗脱13.5分钟。
■结果表明,该方法具有良好的精密度,准确度,recovery,和线性。MBO的线性范围为2.5-250ng/mL,PZQ为10-1000ng/mL,C-4-OH-PZQ,和T-4-OH-PZQ。所测试组件的日内和日间精度CV值在15%以内。4种成分的提取回收率为98.09%~107.46%。血浆中的分析物在室温下保持稳定6小时,在自动进样器(4°C)中26小时,冻融(-20°C)循环后,在-20°C的冰箱中放置60天。方法灵敏度足以评估MBO的药代动力学参数,PZQ,C-4-OH-PZQ,和血浆样品中的T-4-OH-PZQ,MBO的LLOQ为2.5ng/mL,PZQ为10ng/mL,C-4-OH-PZQ,和T-4-OH-PZQ。
■在这项研究中,一种选择性和灵敏的同时定量MBO的LC-MS/MS方法,PZQ,C-4-OH-PZQ,开发并验证了猫血浆中的T-4-OH-PZQ。该方法已成功应用于MBO的药代动力学评价,PZQ,C-4-OH-PZQ,和T-4-OH-PZQ在猫中单次口服施用8mgMBO和20mgPZQ后。
UNASSIGNED: Milbemycin oxime (MBO) and
praziquantel (PZQ) have a broad spectrum of biological activity and are commonly used to treat the parasitic infection in the veterinary clinic. In this study, a fast and efficient LC-MS/MS method was established and validated for the simultaneous determination of MBO, PZQ, cis-4-hydroxylated-PZQ (C-4-OH-PZQ) and trans-4-hydroxylated-PZQ (T-4-OH-PZQ) and in cat plasma.
UNASSIGNED: Extraction of analytes and internal standards from cat plasma by acetonitrile protein precipitation, allows rapid processing of large batches of samples. MBO, PZQ, C-4-OH-PZQ, T-4-OH-PZQ, and internal standard (IS) were eluted for 13.5 min on a C18 column with a 0.1% formic acid water/acetonitrile mixture as the mobile phase.
UNASSIGNED: Results showed that the method had good precision, accuracy, recovery, and linearity. The linearity range was 2.5-250 ng/mL for MBO, and 10-1000 ng/mL for PZQ, C-4-OH-PZQ, and T-4-OH-PZQ. The intra-day and inter-day precision CV values of the tested components were within 15%. The extraction recoveries of the four components ranged from 98.09% to 107.46%. The analytes in plasma remained stable for 6 h at room temperature, 26 h in the autosampler (4 °C), after freeze-thaw (-20°C) cycles, and 60 days in a -20°C freezer. Method sensitivity sufficed for assessing pharmacokinetic parameters of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ in plasma samples with LLOQ of 2.5 ng/mL for MBO and 10 ng/mL for PZQ, C-4-OH-PZQ, and T-4-OH-PZQ.
UNASSIGNED: In this study, a selective and sensitive LC-MS/MS method for the simultaneous quantification of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ in cat plasma was developed and validated.This method had been successfully applied to evaluate the pharmacokinetics of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ after a single oral administration of 8 mg MBO and 20 mg PZQ in cats.