兔脑脊液中万古霉素LC-MS/MS测定方法的建立及其与冰片合用的药动学研究

Development of LC-MS/MS for the Quantitation of Vancomycin in Rabbit Cerebrospinal Fluid and Its Application in Pharmacokinetic Study of Co-administrated with Borneol

关键词:  万古霉素  冰片  血脑屏障  药动学

Key words:  vancomycin  borneol  blood brain barrier  pharmacokinetics

摘要:

目的 建立一种快速灵敏的LC-MS/MS用于兔脑脊液中万古霉素的测定，并进行万古霉素的药动学研究。方法 观察兔分别单独静脉注射万古霉素以及先灌胃给予冰片再静脉注射给予万古霉素后脑脊液中万古霉素的浓度变化。采用内标法进行定量分析，获得脑脊液中万古霉素的浓度，并采用DAS药动学软件拟合主要动力学参数AUC、C_max、T_1/2等。结果 脑脊液中万古霉素的批间精密度为4.7%~6.1%，批内精密度为1.4%~7.1%，准确度为93.6%~106.0%。万古霉素的线性范围为50~5 000 ng·mL^-1，标准曲线的相关系数r>0.99。合用冰片组兔脑脊液中万古霉素的AUC和C_max值明显高于单用万古霉素组。结论 该方法适用于万古霉素在兔脑脊液中的药动学研究。冰片可以提高万古霉素透过血脑屏障的能力。

Abstract:

OBJECTIVE To develop a rapid, highly sensitive and selective performance LC-MS/MS for the determination of vancomycin in rabbit cerebrospinal fluid. Explore and complete the pharmacokinetic study of vancomycin in rabbits. METHODS The concentration of vancomycin in the cerebrospinal fluid was observed after intravenous injection of vancomycin in rabbits and intragastric administration of borneol followed by intravenous injection of vancomycin. Internal standard method was used in analysis to quantify the vancomycincerebrospinal fluid concentration. DAS software was used to obtain kinetic parameters such as AUC, C_max, and T_1/2. RESULTS The inter-day precision of vancomycin in rabbit cerebrospinal fluid was in the range of 4.7%-6.1%, the intra-day precision was in the range of 1.4%-7.1% and the accuracy was in the range of 93.6%-106.0%, respectively. Linear calibration curves for vancomycin was observed at 50-5 000 ng·mL^-1 with correlation coefficient r >0.99. The AUC and C_max values of vancomycin in borneol and vancomycin administrated group were both significantly higher than that in vancomycin single administrated group. CONCLUSION This method is successfully applied in the rabbit cerebrospinal fluid concentration determination of vancomycin. Borneol can improve the ability of vancomycin to penetrate the blood brain barrier.