Zhang Jili, Bai Yubin, Li Bing, Zhou Xuzheng, Si Hongfei, Zhang Jiyu
Key Laboratory of Veterinary Pharmaceutical Development, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Ministry of Agriculture, Lanzhou, Gansu Province, 730050, People's Republic of China.
Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou, Gansu Province, People's Republic of China.
BMC Vet Res. 2019 Jun 24;15(1):210. doi: 10.1186/s12917-019-1963-0.
Oxyclozanide is an anthelmintic drug that is widely used to treat fasciolosis. However, the pharmacokinetics of oxyclozanide in cattle are not yet clearly understood. The present study was designed to develop a sensitive method to determine oxyclozanide levels in cattle plasma using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and to study its pharmacokinetics for application in cattle.
A simple and rapid HPLC-MS/MS analytical method was established and validated to quantify oxyclozanide levels in cattle plasma using niclosamide as the internal standard (IS) in negative ion mode. Chromatographic separation of the analytes was achieved using a C analytical column (75 × 4.6 mm, 2.7 μm) at 30 °C. The mobile phase comprised 0.01% v/v acetic acid (HOAc) diluted in water:acetonitrile (MeCN) (90:10% v/v) and 5 mM ammonium formate in methanol (MeOH):MeCN (75:25, v/v) at a 10:90 ratio (v/v) and was delivered at a flow rate of 0.4 mL min. A good linear response across the concentration range of 0.02048-25.600 μg/mL was achieved (r = 0.994). The method was validated with respect to linearity, matrix effect, accuracy, precision, recovery and stability. The lower limit of quantification (LLOQ) was 0.020 μg/mL, and the extraction recovery was > 98% for oxyclozanide. The inter- and intra-day accuracy and precision of the method showed the relative standard deviation (RSD) less than 10%. The method was successfully applied to an assessment of the pharmacokinetics of oxyclozanide in cattle plasma. In healthy cattle, a single oral dose of an oxyclozanide suspension followed the one-compartment model, with a half-life (T) of 64.40 ± 30.18 h, a plasma clearance rate (CL/F) of 11.426 ± 2.442 mL/h/kg, and an average area under the curve (AUC) of 965.608 ± 220.097 h*μg/mL. The peak concentration (C) was 15.870 ± 2.855 μg/mL, which occurred at a peak time (T) = 22.032 ± 3.343 h.
A reliable, accurate HPLC-MS/MS analytical method was established in our study and successful applied to study the pharmacokinetics of oxyclozanide in cattle plasma. These results will be useful for further evaluations of the pharmacokinetic properties of oxyclozanide or for monitoring therapeutic drugs in animals.
奥昔氯唑胺是一种广泛用于治疗肝片吸虫病的驱虫药。然而，奥昔氯唑胺在牛体内的药代动力学尚未完全明确。本研究旨在建立一种灵敏的方法，使用高效液相色谱-串联质谱法（HPLC-MS/MS）测定牛血浆中奥昔氯唑胺的含量，并研究其药代动力学，以便应用于牛。
建立并验证了一种简单快速的HPLC-MS/MS分析方法，以氯硝柳胺为内标（IS），在负离子模式下定量牛血浆中奥昔氯唑胺的含量。使用C分析柱（75×4.6 mm，2.7μm）在30℃下实现了分析物的色谱分离。流动相由0.01% v/v乙酸（HOAc）稀释于水：乙腈（MeCN）（90:10% v/v）以及5 mM甲酸铵于甲醇（MeOH）：MeCN（75:25，v/v）按10:90比例（v/v）组成，并以0.4 mL/min的流速输送。在0.02048 - 25.600μg/mL的浓度范围内实现了良好的线性响应（r = 0.994）。该方法在线性、基质效应、准确性、精密度、回收率和稳定性方面得到了验证。定量下限（LLOQ）为0.020μg/mL，奥昔氯唑胺的提取回收率> 98%。该方法的日间和日内准确性及精密度显示相对标准偏差（RSD）小于10%。该方法成功应用于评估奥昔氯唑胺在牛血浆中的药代动力学。在健康牛中，单次口服奥昔氯唑胺混悬液符合单室模型，半衰期（T）为64.40±30.18 h，血浆清除率（CL/F）为11.426±2.442 mL/h/kg，平均曲线下面积（AUC）为965.608±220.097 h*μg/mL。峰浓度（C）为15.870±2.855μg/mL，出现在峰时间（T）= 22.032±3.343 h。
本研究建立了一种可靠、准确的HPLC-MS/MS分析方法，并成功应用于研究奥昔氯唑胺在牛血浆中的药代动力学。这些结果将有助于进一步评估奥昔氯唑胺的药代动力学特性或监测动物体内的治疗药物。
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