摘要
目的建立并验证液相色谱-串联质谱法(LC-MS/MS)检测替考拉宁血浆浓度,并分析我院不同负荷方案骨髓炎患者的替考拉宁谷浓度(C_(min))达标情况。方法建立LC-MS/MS法测定替考拉宁的C_(min),考察方法的专属性、标准曲线、精密度与回收率、基质效应和稳定性。收集43例接受替考拉宁治疗的骨髓炎患者,根据给药方案不同分为2组:试验组A患者接受3次负荷剂量400 mg,q12h,试验组B患者接受6次负荷剂量400 mg,q12h,同时进行治疗药物监测(TDM)。两组均于第4天维持剂量给药前30 min采样,检测患者替考拉宁C_(min)值,比较两组替考拉宁C_(min)达标情况。结果血浆中替考拉宁标准曲线方程为Y=0.0324X+0.000886(r=0.9964),在0.20~50.00μg·m L^(-1)内线性关系良好;质控样本的准确度为94.71%~112.50%内;日内、日间RSD为3.17%~15.19%;提取回收率为81.22%~91.26%;基质效应为93.54%~119.78%。临床应用中,试验组A负荷剂量后替考拉宁平均C_(min)为(8.32±4.76μg·mL^(-1),C_(min)≥10μg·mL^(-1)比例仅为25.90%;试验组B负荷剂量后替考拉宁平均C_(min)为(19.58±7.78)μg·mL^(-1),16例患者C_(min)均≥10μg·mL^(-1);两组平均C_(min)差异有统计学意义(P<0.0001)。结论建立的LC-MS/MS方法适用于替考拉宁常规TDM。临床应用中,低频次负荷方案下替考拉宁C_(min)达标情况较差,而TDM指导的高频次负荷方案下替考拉宁C_(min)达标情况更优。研究表明替考拉宁TDM的重要性,尤其是针对感染高危患者人群。
Objective To establish and validate a liquid chromatography-mass spectrometry(LC-MS/MS)method for the detection of teicoplanin concentration in plasma,and to analyze the achievement of teicoplanin trough concentrations(C_(min))in patients with osteomyelitis at different loading doses in General Hospital of Eastern Theater Command of the PLA.Methods To establish an LC-MS/MS method for the determination of teicoplanin C_(min)and investigate the specificity,standard curve,precision and recovery,matrix effect and stability of the method.43 patients with osteomyelitis treated with teicoplanin were divided into two groups according to the dosing regimen:test group A received three loading doses of 400 mg,q12h and test group B received six loading doses of 400 mg,q12h,along with multiple therapeutic drug monitoring(TDM).In both groups,samples were collected 30 min before the maintenance dose on day four to detect teicoplanin C_(min)values in patients and teicoplanin C_(min)targets were compared between two groups.Results The standard curve equation of teicoplanin in plasma was Y=0.0324X+0.000886(r=0.9964),and the linear relationship was good within 0.20-50.00μg·mL^(-1);the accuracy of quality control samples was 94.71%-112.50%;the intra-day and inter-day RSDs were 3.17%-15.19%;the extraction recoveries were 81.22%-91.26%;and the matrix effect was 93.54%-119.78%.In clinical application,the mean C_(min)of teicoplanin after loading dose in test group A was(8.32±4.76)μg·mL^(-1),and the proportion of C_(min)≥10μg·mL^(-1)was only 25.90%;the mean C_(min)of teicoplanin after loading dose in test group B was(19.58±7.78)μg·mL^(-1),and C_(min)was≥10μg·mL^(-1)in all 16 patients.There was a significant difference in mean C_(min)between two groups(P<0.0001).Conclusion The LC-MS/MS method developed in this trial is suitable for routine TDM with teicoplanin.In clinical practice,teicoplanin C_(min)compliance was poor with low-frequency loading regimens,while teicoplanin C_(min)compliance was superior with TDM-guided high
作者
俞慧敏
岳慧杰
钱红波
张晏洁
何志伟
周青
Hui-Min YU;Hui-Jie YUE;Hong-Bo QIAN;Yan-Jie ZHANG;Zhi-Wei HE;Qing ZHOU(Department of Clinical Pharmacy,General Hospital of Eastern Theater Command of the PLA,Nanjing 210002,China;Department of Orthopedics,General Hospital of Eastern Theater Command of the PLA,Nanjing 210002,China)
出处
《中国药师》
CAS
2023年第10期51-58,共8页
China Pharmacist
基金
国家自然科学基金青年科学基金项目(81901890)。
