万古霉素治疗药物监测中不同牛血清替代人血清可行性分析

Feasibility Analysis of Different Bovine Serum Replacing Human Serum in Therapeutic Drug Monitoring of Vancomycin

目的分析万古霉素治疗药物监测(TDM)中不同牛血清替代人血清作为空白基质的可行性。方法建立测定万古霉素血药浓度的高效液相色谱(HPLC)法。收集医院2022年1月至2023年1月接受万古霉素治疗患者的血清样本105份(已检测血药浓度),关联人血清和不同厂家(厂家1和厂家2)的不同牛血清(小牛血清、新生牛血清、胎牛血清)作为空白基质的标准曲线,得到相应的血药浓度。采用Passing-Bablok回归分析法和Bland-Altman法考察测定结果的相关性和一致性。结果以人血清和不同牛血清作为空白基质时,万古霉素质量浓度在1~100 mg/L范围内与峰面积线性关系均良好(R^(2)>0.999);日内精密度、日间精密度的RSD均小于15%,相对回收率均在85%~115%范围内。人血清与不同牛血清作为空白基质均有良好的相关性(r>0.999),但均有系统误差和比例误差。厂家1的3种牛血清(小牛血清1、新生牛血清1、胎牛血清1)对比人血清作为空白基质检测值的相对平均偏差和95%一致性界限均小于50%允许总误差(±15%),厂家2的3种牛血清(小牛血清2、新生牛血清2、胎牛血清2)对比人血清作为空白基质检测值的相对平均偏差或95%一致性界限超出±15%。结论使用HPLC法进行万古霉素TDM时,部分厂家生产的牛血清能替代人血清作为空白基质进行检测。

Objective To analyze the feasibility of different bovine serum replacing human serum as blank substrate in the therapeutic drug monitoring(TDM)of vancomycin.Methods The high-performance liquid chromatography(HPLC)method for determining the plasma concentration of vancomycin was established.A total of 105 serum samples(plasma concentration had been tested)from patients receiving vancomycin treatment in a hospital from January 2022 to January 2023 were collected,the vancomycin plasma concentration of human serum and different bovine serum(calf serum,newborn calf serum,fetal calf serum)from manufacturers 1 and 2 was obtained through the correlation of the vancomycin plasma concentration of above serum samples and the standard curves of human serum and bovine serum as the blank substrate.The Passing-Bablock regression analysis and the Bland-Altman method were used to explore the correlation and consistency of the measurement results.Results When human serum and different bovine serum as the blank substrate,the linear range of vancomycin was 1-100 mg/L(R^(2)>0.999).The RSDs of intra-day precision and inter-day precision were lower than 15%,and the relative recovery rate of vancomycin was in the range of 85%to 115%.The correlation of human serum with different bovine serum as blank substrate was good(r>0.999),but with systematic and proportional errors.The relative average deviations and 95%limits of agreement(95%LoA)of the detection values of three bovine serum from manufacturer 1(calf serum 1,newborn calf serum 1,fetal calf serum 1)compared to human serum as the blank substrate were all lower than the 50%of total allowable error(±15%),while the relative average deviations or 95%LoA of the detection values of three bovine serum from manufacturer 2(calf serum 2,newborn calf serum 2,fetal calf serum 2)compared to human serum as the blank substrate were over±15%.Conclusion In the TDM of vancomycin by HPLC,the bovine serum produced by some manufacturers can replace human serum as the blank substrate for detection.