LC-MS/MS法测定人血浆中卡泊芬净浓度及危重症感染患者血浆中卡泊芬净浓度监测

【作者】 杨乾婷； 王陶陶； 谢姣； 陈璐； 程晓亮； 董海燕； 董卫华； 魏友霞； 王雪； 董亚琳；

【机构】 西安交通大学第一附属医院药剂科； 西安交通大学第一附属医院中心ICU；

【摘要】 目的:卡泊芬净通常被用于治疗侵袭性真菌感染的危重症感染（ICU）患者,而ICU患者之间的PK参数差异较大,所以本研究的目的是监测ICU患者卡泊芬净血药浓度,研究其谷浓度变化特征及其与目标浓度以及临床疗效之间的关系。方法:建立卡泊芬净血药浓度测定的方法学（LC-MS/MS）并对其进行验证,应用已建立的方法监测18例ICU患者的卡泊芬净谷值血药浓度（共42份血样）。结果:卡泊芬净在0.05～20 mg/L范围内线性良好（r²=0.9994）,平均回收率85.2%～95.3%,基质效应98.1%～107.0%,日内、日间精密度的RSD小于5.5%且准确度范围为96.2～102.3%。另外,研究发现卡泊芬净在ICU患者中平均血浆谷值浓度为2.13±0.99 mg/L （变化范围:0.51～3.79 mg/L）。这些患者中,13例为念珠菌感染患者,5例为曲霉菌感染患者。在13例念珠感染患者中有1 1例卡泊芬净血浆谷值浓度大于1 mg/L ((念珠菌的最小抑菌浓度(MIC₉₀)),而这11例中有10例临床有效。13例中2例患者卡泊芬净谷值浓度小于1 mg/L并且都临床治疗无效。5例曲霉菌感染患者的卡泊芬净谷值浓度都大于0.5 mg/L （曲霉菌的最小抑菌浓度）,但只有2例临床有效。讨论:实验建立的LC-MS/MS快速、灵敏并且可重复,可用于临床ICU患者卡泊芬净的血药浓度监测且实验发现ICU患者卡泊芬净血药浓度个体间差异大。当卡泊芬净谷值浓度大于MIC₉₀时,可能会获得较好的临床效果。更多还原

【Abstract】 Objectives:Caspofungin is common used for treatment of fungal infections in intensive care unit（ICU） patients and the pharmacokinetics（PK） of caspofungin in ICU patients may be highly variable,so we determine to measure caspofungin trough levels(C_min) and analyze the association between troughs and efficacy in ICU patients.Methods:A rapid and sensitive liquid chromatography-tandem mass spectrometry（LC-MS/MS） method was established and validated for measuring caspofungin C_min and 42 samples from 18 ICU patients were monitored.Results:The calibration curve included the clinically relevant caspofungin concentration ranged from 0.05 to 20 mg/L and exhibited excellent linearity.The mean recovery ranged from85.2 to 95.3% and the matrix effect from 98.1 to 107.0%.The intra-and inter-day precisions were <5.5% and their accuracies were within the range of 96.2～102.3%.The mean value of caspofungin C_min was 2.13±0.99 mg/L（range:0.51～3.79 mg/L）.The patients were infected by Candida spp.（13） and Aspergillus spp.（5）,respectively.84.6%（11/13） patients who were infected by Candida spp.were found to have caspofungin C_minabove 1 mg/L(MIC₉₀ for Candida spp.) and 10 of the 11 patients achieved clinical success.The other 2 patients were found to have caspofungin C_min below 1 mg/L and didn’t show clinical improvement.All of the 5 patients who were infected by Aspergillus spp.were found to have plasma caspofungin C_min above 0.5 mg/L(MIC₉₀ for Aspergillus spp.),but only 2 achieved clinical success.Discussion:the validated LC-MS/MS method is rapid,sensitive and reproducible,which is suite to monitor the concentration of caspofungin.Caspofungin C_min ranges were found to be relatively wide in ICU patients and relatively good treatment result might be obtained when C_min> MIC₉₀.更多还原