The Third Clinical Institute Affiliated to Wenzhou Medical University & Wenzhou People's Hospital, Wenzhou 325000, China.
Analytical and Testing Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
Biomed Res Int. 2018 May 23;2018:6562309. doi: 10.1155/2018/6562309. eCollection 2018.
Eighteen Sprague-Dawley rats were randomly divided into three groups: ketamine group, rhynchophylline group, and ketamine combined with rhynchophylline group ( = 6). The rats of two groups received a single intraperitoneal administration of 30 mg/kg ketamine and 30 mg/kg rhynchophylline, respectively, and the third group received combined intraperitoneal administration of 30 mg/kg ketamine and 30 mg/kg rhynchophylline together. After blood sampling at different time points and processing, the concentrations of ketamine and rhynchophylline in rat plasma were determined by the established ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. Chromatographic separation was achieved using a UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 m) with carbamazepine as an internal standard (IS). The initial mobile phase consisted of acetonitrile and water (containing 0.1% formic acid) with gradient elution. Multiple reaction monitoring (MRM) modes of 238.1 → 179.1 for ketamine, 385.3 → 159.8 for rhynchophylline, and 237.3 → 194.3 for carbamazepine (IS) were utilized to conduct quantitative analysis. Calibration curve of ketamine and rhynchophylline in rat plasma demonstrated good linearity in the range of 1-1000 ng/mL (r > 0.995), and the lower limit of quantification (LLOQ) was 1 ng/mL. Moreover, the intra- and interday precision relative standard deviation (RSD) of ketamine and rhynchophylline were less than 11% and 14%, respectively. This sensitive, rapid, and selective UPLC-MS/MS method was successfully applied to pharmacokinetic interaction study of ketamine and rhynchophylline after intraperitoneal administration. The results showed that there may be a reciprocal inhibition between ketamine and rhynchophylline.
十八只 Sprague-Dawley 大鼠被随机分为三组：氯胺酮组、钩藤碱组和氯胺酮联合钩藤碱组（每组 6 只）。两组大鼠分别单次腹腔注射 30mg/kg 氯胺酮和 30mg/kg 钩藤碱，第三组大鼠同时腹腔注射 30mg/kg 氯胺酮和 30mg/kg 钩藤碱。在不同时间点采血并处理后，采用建立的超高效液相色谱-串联质谱法（UPLC-MS/MS）测定大鼠血浆中氯胺酮和钩藤碱的浓度。色谱分离采用 UPLC BEH C18 柱（2.1mm×50mm，1.7μm），以卡马西平为内标（IS）。初始流动相为乙腈和水（含 0.1%甲酸），梯度洗脱。采用多反应监测（MRM）模式，对氯胺酮（238.1→179.1）、钩藤碱（385.3→159.8）和卡马西平（IS，237.3→194.3）进行定量分析。氯胺酮和钩藤碱在大鼠血浆中的标准曲线在 1-1000ng/mL 范围内呈良好线性（r＞0.995），定量下限（LLOQ）为 1ng/mL。此外，氯胺酮和钩藤碱的日内和日间精密度相对标准偏差（RSD）均小于 11%和 14%。该灵敏、快速、选择性的 UPLC-MS/MS 方法成功应用于氯胺酮和钩藤碱腹腔给药后的药代动力学相互作用研究。结果表明，氯胺酮和钩藤碱之间可能存在相互抑制作用。
