摘要
目的建立高效液相色谱法同时测定人血浆中利奈唑胺及其主要代谢物PNU-142300和PNU-142586浓度,用于危重症患者血药浓度监测。方法以氯霉素为内标,酸化乙腈(含体积分数0.1%甲酸)为蛋白沉淀剂,双溶剂流动相为A乙腈、B枸橼酸(0.1 mol·L^(-1))-磷酸氢二钠(0.2 mol·L^(-1))缓冲溶液(pH 3.0),色谱柱为Diamonsil C_(18)柱(4.6 mm×250 mm,5μm),流速0.5 mL·min^(-1),梯度洗脱,检测波长254 nm,柱温30℃,进样量20μL。结果利奈唑胺在0.5~40μg·mL^(-1)的浓度范围内线性关系良好(r=0.9999),定量下限为0.5μg·mL^(-1),检测限为0.1μg·mL^(-1);PNU-142300和PNU-142586在0.5~20μg·mL^(-1)的浓度范围内线性关系良好(r=0.9998和r=0.9996),定量下限为0.5μg·mL^(-1),检测限为0.2μg·mL^(-1)。10例重症患者中肾功能不全患者血浆利奈唑胺及代其谢物PNU-142300和PNU-142586暴露量分别为肾功能正常患者的3.62、1.88和2.30倍,且利奈唑胺及其代谢物暴露量与血小板减少和贫血间具有较强的相关性。结论该方法操作简便,灵敏、准确度高,可用于重症患者利奈唑胺及其代谢物PNU-142300和PNU-142586临床血药浓度监测和不良反应相关性研究。
OBJECTIVE To establish a high-performance liquid chromatography method for simultaneous determination of linezolid and its main metabolites PNU-142300 and PNU-142586 in human plasma,and monitor the blood concentration of critically ill patients.METHODS The determination was performed on Diamonsil C_(18)column(4.6 mm×250 mm,5μm)with chloramphenicol as internal standard,acidified acetonitrile as protein precipitator,and bisolvent mobile phase consisting of A acetonitrile,B citric acid(0.1 mol·L^(-1))-sodium hydrogen phosphate(0.2 mol·L^(-1))buffer solution(pH 3.0).The flow rate was 0.5 mL·min^(-1),the detection wavelength was set at 254 nm,the column temperature was maintained at 30℃,and the sample size was 20μL.RESULTS Linezolid had a good linear relationship in the concentration range of 0.5-40μg·mL^(-1)(r=0.9999).The lower limit of quantitation was 0.5μg·mL^(-1),and the detection limit was 0.1μg·mL^(-1).PNU-142300 and PNU-142586 had good linear relationship in the concentration range of 0.5-20μg·mL^(-1)(r=0.9998 and r=0.9996),the lower limit of quantitation was 0.5μg·mL^(-1),and the detection limit was 0.2μg·mL^(-1).In 10 critically ill patients,plasma linezolid and PNU-142300 and PNU-142586 were 3.62,1.88 and 2.30 times higher in patients with renal insufficiency than in patients with normal renal function,respectively.There was a strong correlation between exposure of linezolid and its metabolites and thrombocytopenia and anemia.CONCLUSION The method is simple,sensitive,and accurate,and can be used to monitor the blood concentration of linezolid and its metabolites PNU-142300 and PNU-142586 in critically ill patients and study the correlation of adverse reactions.
作者
苟军强
李倩
周晓丽
范宁
李萌
王晓锋
尹东锋
GOU Junqiang;LI Qian;ZHOU Xiaoli;FAN Ning;LI Meng;WANG Xiaofeng;YIN Dongfeng(College of Pharmacy,Shihezi University,Shihezi 832003,China;Department of Pharmacy,General Hospital of Xinjiang Military Command,Urumqi 830000,China)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2024年第8期732-737,共6页
Chinese Pharmaceutical Journal
