Male Sprague-Dawley rats () were randomly divided into three groups: a saline group (20 mL/kg by gavage), a ketamine (KET) group (100 mg/kg by gavage), and a KET (the same routes and doses) combined with levo-tetrahydropalmatine (L-THP; 40 mg/kg by gavage) group (). Blood samples were acquired at different time points after drug administration. A simple and sensitive ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to determine the concentrations of KET and its metabolite, norketamine (NK), in rat plasma. Chromatographic separation was achieved using a BEH C18 column (, 1.7 μm) with chlorpheniramine maleate (Chlor-Trimeton) as an internal standard (IS). The initial mobile phase consisted of acetonitrile–water with 0.1% methanoic acid (80 : 20, ). The multiple reaction monitoring (MRM) modes of m/z 238.1→m/z 179.1 for KET, m/z 224.1→m/z 207.1 for NK, and m/z 275→m/z 230 for Chlor-Trimeton (IS) were utilized to conduct a quantitative analysis. Calibration curves of KET and NK in rat plasma demonstrated good linearity in the range of 2.5–500 ng/mL (), and the lower limit of quantification (LLOQ) was 2.5 ng/mL for both. Moreover, the intra- and interday precision relative standard deviation (RSD) of KET and NK were less than 4.31% and 6.53%, respectively. The accuracies (relative error) of KET and NK were below -1.41% and -6.07%, respectively. The extraction recoveries of KET and NK were more than % and %, respectively. This sensitive, rapid, and selective UPLC-MS/MS method was successfully applied to study the pharmacokinetic effects of L-THP on KET after gastric gavage. The results demonstrated that L-THP could increase the bioavailability of KET and promote the metabolism of KET. The results showed that L-THP has pharmacokinetics effects on KET in rat plasma.

中文翻译：

---

超高效液相色谱串联质谱法研究四氢巴马汀对大鼠血浆氯胺酮的药代动力学作用。

雄性Sprague-Dawley大鼠（）随机分为三组：生理盐水组（20 mL / kg灌胃），氯胺酮（KET）组（100 mg / kg灌胃）和KET（相同途径和剂量）联合左旋四氢巴马汀（ L -THP;灌胃40 mg / kg）组（）。给药后的不同时间采集血样。建立了一种简单灵敏的超高效液相色谱串联质谱法（UPLC-MS / MS），用于测定大鼠血浆中KET及其代谢产物去甲氯胺酮（NK）的浓度。色谱分离使用BEH C18柱（（ 1.7 微米），以马来酸氯苯那敏（Chlor-Trimeton）作为内标（IS）。最初的流动相包括乙腈-水和0.1％的甲醇酸（80:20，）。KET的m / z 238.1→m / z 179.1，NK的m / z 224.1→m / z 207.1，Chlor-Trimeton（IS）的m / z 275→m / z 230的多反应监测（MRM）模式被用来进行定量分析。大鼠血浆中KET和NK的校准曲线在2.5–500 ng / mL的范围内显示出良好的线性（），两者的定量下限（LLOQ）均为2.5 ng / mL。此外，KET和NK的日内和日间精确度相对标准偏差（RSD）分别小于4.31％和6.53％。KET和NK的准确度（相对误差）分别低于-1.41％和-6.07％。KET和NK的提取回收率均大于。％和 ％， 分别。这种灵敏，快速，选择性的UPLC-MS / MS方法已成功应用于研究L - THP对胃管灌胃后KET的药代动力学作用。结果表明，L - THP可以增加KET的生物利用度并促进KET的代谢。结果表明，L - THP对大鼠血浆中的KET具有药代动力学作用。