肝素钠注射液对美罗培南在腹膜透析液中的稳定性影响

Effect of heparin sodium injection on the stability of meropenem in peritoneal dialysis solution

目的:考察肝素钠注射液对美罗培南在腹膜透析液中的稳定性影响。方法:利用高效液相色谱法测定美罗培南的含量。色谱条件:采用Sunfire C_(18)色谱柱(250 mm×4.6 mm,5μm),以乙腈-0.05 mol·L^(-1)磷酸二氢钾(pH 6.5,8∶92)为流动相,流速1.0 mL·min^(-1),检测波长298 nm。考察在37℃下含或不含肝素钠注射液的美罗培南腹膜透析液放置30 h的外观性状、pH及含量。结果:在本方法中,美罗培南检测浓度线性范围为0.1~1.0 mg·mL^(-1)(r=0.999 7);平均加样回收率为96.5%,RSD为2.2%。9 h内任何一袋透析液的颜色均未发生改变,第12 h起颜色均变成微黄色,含肝素钠注射液的腹膜透析液颜色变化更明显。整个过程中,两组透析液均未见混浊、沉淀,pH无明显变化。在不含肝素钠注射液的腹膜透析液中,美罗培南的稳定性可达6 h;在含肝素钠注射液的腹膜透析液中,美罗培南的稳定性仅有3 h。结论:所建立的含量测定方法简单、准确、灵敏,可用于腹膜透析液中美罗培南的含量测定;37℃条件下,1.0 g美罗培南在不含肝素钠注射液的腹膜透析液(乳酸盐-G1.5%)中6 h内是稳定的,对治疗腹膜透析相关性腹膜炎是有效的;在含肝素钠注射液的腹膜透析液(乳酸盐-G1.5%)中美罗培南的稳定性仅有3 h,可能会影响临床疗效。

Objective：To determine the effect of heparin sodium injection on the stability of meropenem in peritoneal dialysis solution.Methods：HPLC method was adopted to determine the content of meropenem.A Sunfire C18 column（250 mm×4.6 mm,5μm）was used for the separation,with mobile phase consisted of acetonitrile-0.05 mol·L^（-1） potassium phosphate buffer（pH 6.5,8：92）at the flow rate of 1.0 mL·min^（-1）.The detection wavelength was 298 nm.Meropenem in dialysates solutions with and without heparin was investigated over 30 hours in terms of appearance,pH value and content at 37℃.Results：The linear range of meropenem was 0.1-1.0 mg·mL^（-1）（r=0.999 7）with an average recovery of 96.5%（RSD=2.2%,n=9）.Colors of the test peritoneal dialysis solutions did not change in 9 hours and all turned to be slightly yellow after 12 hours.The color of heparinized meropenem solutions was yellower than that of nonheparinized meropenem solutions.No haziness or precipitation was observed in any of the test peritoneal dialysis solutions.The pH did not change substantially in any solution throughout the study.Meropenem was stable（≥90%of the initial concentration）in non-heparinized peritonealdialysis solution for up to 6 hours at 37℃.However,meropenem was stable in herparinized peritoneal dialysis solution for only 3 hours at 37℃.Conclusion：The established method was simple,accurate and sensitive.It was suitable for the content determination of meropenem in peritoneal dialysis solution.Meropenem（1.0 g）was considered stable innon-heparinized peritoneal dialysis solution（containing glucose 1.5%）at 37℃for 6 hours and that was effective in the treatment of peritonitis associated with peritoneal dialysis.Meropenem was considered stable in heparinized peritoneal dialysis solution（containing glucose 1.5%）at 37℃for only 3 hours,which may affect the efficacy of the therapy.