摘要
目的建立超高效液相色谱-串联质谱(UPLC-MS/MS)方法检测血浆咖啡因浓度,评价咖啡因药物浓度监控(TDM)在早产儿呼吸窘迫综合征(RDS)治疗中的临床应用价值。方法取血浆样本于离心管中,加入咖啡因氘代同位素内标,再加入蛋白沉淀剂,充分涡旋混合后,离心取上层清液进入质谱分析。流动相为甲醇和水,梯度洗脱;柱温45℃,使用岛津LC-30AD-CL液相系统和AB SCIEX 4500 QTRAP质谱仪建立方法,并对该方法的敏感度、特异度、线性、准确度、不精密度、基质效应、携带污染进行评估。纳入2021年2至4月就诊于武汉大学人民医院新生儿科诊断为新生儿RSD的患者30例,检测不同RDS早产儿相同给药方案下的咖啡因谷值浓度以评估个体变异对咖啡因药物浓度的影响。结果咖啡因的检出限为0.02μg/ml,最低定量限为0.05μg/ml,在1.0~100.0μg/ml浓度范围内表现出良好的线性(R^(2)=0.9986,R>0.99)、特异度(回收率85.52%~114.12%)、准确度(回收率85.97%~114.53%)、日内和日间不精密度(CV 6.01%~11.28%),基质效应和携带污染可忽略不计。检测30例RSD早产儿相同给药方案(10 mg/kg)后的咖啡因谷值浓度为(25.45±11.61)μg/ml,变异系数为44.88%。结论成功建立了一种UPLC-MS/MS方法用于监测咖啡因血药浓度。咖啡因TDM具有一定的临床应用价值,可用于辅助RDS诊疗,提高咖啡因疗效。
Objective To establish an ultra-high-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for plasma caffeine concentration detection,and to explore the clinical value of caffeine therapeutic drug monitoring(TDM)in the treatment of premature infants with respiratory distress syndrome(RDS).Method Take the plasma sample in a centrifuge tube,add the caffeine deuterated isotope internal standard,then add the protein precipitant,vortex the mixture thoroughly,and centrifuge the supernatant to enter the mass spectrometry analysis.The mobile phase were methanol and water,gradient elution;the column temperature was 45℃,the method was established using Shimadzu LC-30AD-CL liquid system and AB SCIEX 4500 QTRAP mass spectrometer,and the sensitivity,specificity,linearity,accuracy imprecision,matrix effect,and carry-over of the method were evaluated.Sample from 30 patients diagnosed with neonatal RSD were collected in the Department of Neonatology of Renmin Hospital of Wuhan University from February to April 2021,then detected the trough concentration of caffeine in premature infants with RDS after taking the same dose of caffeine to assess the impact of individual variation on caffeine drug concentration.Results The detection limit of caffeine was 0.02μg/ml,and the lowest limit of quantification was 0.05μg/ml.It showed good linearity(R^(2)=0.9986,R>0.99)in the concentration range from 1.0 to 100.0μg/ml,specificity(recovery rate of 85.52%-114.12%),accuracy(recovery rate 85.97%-114.53%),intra-day and inter-day imprecision(CV 6.01%-11.28%),matrix effects and carryover pollution were negligible.The trough concentration of 30 preterm infants with RSD after taking the same dose of caffeine(10 mg/kg)was(25.45±11.61)μg/ml,and the coefficient of variation was 44.88%.Conclusion This study established an accurate and reliable UPLC-MS/MS method with low sample consumption to monitor the blood concentration of caffeine;caffeine TDM has certain clinical application value,which can be used to assist RDS diagno
作者
乐娟
彭锐
何琪
洪澳
吴鹏
王少亭
方成志
李艳
Le Juan;Peng Rui;He Qi;Hong Ao;Wu Peng;Wang Shaoting;Fang Chengzhi;Li Yan(Medical Laboratory Center,Renmin Hospital of Wuhan University,Wuhan 430060,China;Department of Neonatology,Renmin Hospital of Wuhan University,Wuhan 430060,China)
出处
《中华检验医学杂志》
CAS
CSCD
北大核心
2021年第8期703-708,共6页
Chinese Journal of Laboratory Medicine
关键词
咖啡因
呼吸窘迫综合征
液相色谱-质谱联用
早产儿
药物浓度监控
Caffeine
Respiratory distress syndrome
Liquid chromatography-mass spectrometry
Preterm infants
Drug concentration monitoring
