血浆和腹膜透析液中万古霉素浓度的测定及在腹膜透析相关性腹膜炎患者中的应用

Determination of vancomycin concentration in plasma and peritoneal dialysate and its application in the patients with peritoneal dialysis-related peritonitis

目的:建立测定血浆和腹膜透析液中万古霉素浓度的HPLC法,为腹膜透析相关性腹膜炎患者的药物浓度监测提供参考。方法:采用Waters Symmetry C18色谱柱(250 mm×4.6 mm,5μm),以甲醇∶乙腈∶0.05 mol/L KH2PO4=11∶2∶87为流动相,检测波长236 nm,柱温30℃,流速1.0 ml/min,检测血浆和腹膜透析液中万古霉素的浓度。结果:血浆中的万古霉素浓度在0.2~40μg/ml范围内线性关系良好(r=0.998),定量限为0.2μg/ml,提取回收率为85.11%~89.15%,方法回收率为86.72%~89.51%。腹膜透析液中的万古霉素浓度在0.2~16μg/ml范围内线性关系良好(r=0.999),定量限为0.2μg/ml,提取回收率为88.13%~90.18%,方法回收率为87.10%~103.24%。本研究共纳入36例腹膜透析相关性腹膜炎患者,31例(86.11%)患者的血浆和腹膜透析液中万古霉素浓度达标;而尿量>500 ml/d的患者,其血浆和腹膜透析液中万古霉素浓度偏低。结论:该方法可满足腹膜炎患者的万古霉素浓度监测,对于尿量>500 ml/d的患者,需适当增加万古霉素的剂量并加强监测,以维持安全有效的药物浓度。

Objective:To establish a high performance liquid chromatography(HPLC)method for the determination of vancomycin in human plasma and peritoneal dialysate,so as to provide a methodological basis for clinical monitoring of vancomycin concentration in the patients with peritoneal dialysis-related peritonitis.Methods:Waters Symmetry C18 column(250 mm×4.6 mm,5μm)was applied.The mobile phase was methanol∶acetonitrile∶0.05 mol/L KH2PO4=11∶2∶87 at a flow rate of 1.0 ml/min,the detection wavelength was 236 nm and the column temperature was 30℃.The concentration of vancomycin in plasma and peritoneal dialysate was determined.Results:Vancomycin displayed good linearity within the range of 0.2-40μg/ml(r=0.998)in plasma and the lower limitation of quantification was 0.2μg/ml.The extraction rates were 85.11%-89.15%,and the recovery rates were 86.72%-89.51%.In peritoneal dialysate,vancomycin displayed good linearity within the range of 0.2-16μg/ml(r=0.999)and the lower limitation of quantification was 0.2μg/ml.The extraction rates were 88.13%-90.18%,and the recovery rates were 87.10%-103.24%.Of the 36 patients included in the study,31(86.11%)reached the effective concentration of vancomycin.However,the patients with a urine output of more than 500 ml/d had a lower concentration of vancomycin both in plasma and peritoneal dialysate.Conclusion:The method could meet the need of vancomycin concentration monitoring in the patients with peritonitis.Furthermore,for the patients with a urine output of more than 500 ml/d,vancomycin dosage should be appropriately increased and monitoring should be intensified,so as to ensure a safe and effective drug concentration.