罗哌卡因血浆浓度测定与关节腔给药经时变化

Determination of Ropivacaine in Plasma and the Time Dependent Change of Drug Administration via Articular Cavity

目的建立高效液相色谱(HPLC)法测定血浆中罗哌卡因浓度并观察关节腔给药后体内血药浓度的经时变化。方法以利多卡因作为内标,用乙酸乙酯提取,以乙腈-0.025mol.L-1磷酸缓冲液(pH值3.0)(25:75)为流动相,采用Hypersil ODS(4.6mm×200mm,5μm)分离,检测波长为220nm。人工全膝关节置换术后,关节腔注射罗哌卡因150mg,于注射后0.5,1.0,1.5,2.0,2.5,4.5h取血3mL,测定罗哌卡因浓度。结果在选定的色谱条件下,罗哌卡因与血浆中的杂质及内标物分离良好。罗哌卡因血浆浓度在0.1～4.0μg.mL-1范围内线性关系良好(r=0.9995),最低检测浓度为0.02μg.mL-1(血浆浓度),日内、日间RSD<5%,血浆中罗哌卡因的提取回收率为85.2%～96.2%。关节腔用药后Cmax为(637.5±69.6)μg.L-1,tmax为(1.31±0.31)h。结论该法测定血浆罗哌卡因的血药浓度,操作简便,结果可靠、准确,重复性较好。关节腔单次注射罗哌卡因150mg,其血浓度较低,持续时间较长,为比较安全的给药方法。

Objective A RP-HPLC method for determination of ropivacaine in plasma was developed and was applied to analyze the time dependent change of ropivacaine treated via articular cavity. Methods The sample was treated by adding lidocaine as an internal standard, extraetd with ethyl acetate. Aeetonitrile and 0. 025 mol · L^-1 phosphate buffer solution （pH3.0） （25 ： 75 ） were used as the mobile phase, Hypersil ODS（4.6 mm × 200 mm,5μm）as the stationary phase, and the detection wavelength was 220 nm. After the whole knee arthroplasty, 150 mg ropivaeaine was administered into articular cavity, the concentration of which was determined at the following time, 0.5,1.0,1.5,2.0,2.5,4.5 h. Results Under the selected spectrum condition, ropivacaine was completely separated from the internal standard and the impurities of plasma. The linear range was from 0.1 - 4.0 μg· mL^-1 with r = 0. 999 5. The detection limit was 0. 02 μg - mL^-1. And the relative standard deviation of inner-day and inter-day was less than 5%. The recovery rate of extraction was between 85.2 - 96.2%. The maximum concentration of ropivacaine in the plasma was （637.5 ± 69.6） μg · L^-1 , and the peak of the time was （1.31 -0. 31 ） h. Conclusion The method for determination of ropivacaine in plasma is simple, accurate, reliable and with a good reproducibility. Sigle administration of 150 mg ropivaeaine via articular cavity shows lower drug plasma concentration and longer sustained time, which is a safe way for drug administration.