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多黏菌素B血药浓度的测定及其在重症患者中的应用
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| 篇名： | 多黏菌素B血药浓度的测定及其在重症患者中的应用 |
| TITLE： | Determination of polymyxin B concentration in plasma and its application in critically ill patients |
| 摘要： | 目的 建立测定多黏菌素B血药浓度的方法并应用于临床。方法血浆样品经5%三氯乙酸溶液蛋白沉淀后，以多黏菌素E2为内标，采用超高效液相色谱-串联质谱（UPLC-MS/MS）法测定多黏菌素B1、B2的质量浓度。以BEHC18为色谱柱，以水（含0.1%甲酸）-乙腈（含0.1%甲酸）为流动相进行梯度洗脱，流速为0.5mL/min，进样量为10μL。采用电喷雾离子源以多反应监测模式进行正离子扫描，用于定量分析的离子对分别为m/z603.2→101.2（多黏菌素B1）、595.7→101.1（多黏菌素B2）、578.5→101.1（内标）。采用上述方法测定79例重症患者体内多黏菌素B的血药浓度，记录患者急性肾损伤（AKI）的发生情况并分析多黏菌素B血药浓度与AKI发生的相关性。结果多黏菌素B1、B2检测质量浓度的线性范围分别为200～20000、50～5000ng/mL（r＞0.995），定量下限分别为200、50ng/mL；日内、日间精密度的RSD均不高于12.06%，平均提取回收率为103.04%～117.44%（RSD≤10.45%），基质效应、稳定性试验的RSD均不高于7.42%。79例患者的多黏菌素B稳态谷、峰浓度分别为（2.54±2.52）、（8.17±5.20）mg/L。在被纳入AKI评价的27例患者中，有18例患者（66.67%）发生AKI；未发生AKI患者的多黏菌素B峰浓度显著低于AKI患者（P＜0.05），但两者谷浓度比较差异无统计学意义（P＞0.05）。结论所建UPLC-MS/MS法操作简便、灵敏度高，可用于患者体内多黏菌素B血药浓度的检测；患者AKI的发生可能与体内多黏菌素B的峰浓度有关。 |
| ABSTRACT： | OBJECTIVE To establish a method for the determination of polymyxin B concentration in plasma and apply it to clinical practice. METHODS After precipitated with 5% trichloroacetic acid solution， using polymyxin E2 as internal standard， the concentrations of polymyxin B1 and B2 in plasma sample were determined by UPLC-MS/MS. The determination was performed on BEH C18 chromatographic column with water （0.1% formic acid）-acetonitrile （0.1% formic acid） as mobile phase （gradient elution） at the flow rate of 0.5 mL/min. The sample size was 10 µL. The detection was accomplished with electrospray ionization operated in positive ion scanning by multi-reaction monitoring mode. The ion pairs for quantitative analysis were m/z 603.2→101.2 （polymyxin B1）， m/z 595.7→101.1 （polymyxin B2） and m/z 578.5→101.1 （internal standard）. The plasma concentration of polymyxin B in 79 critically ill patients was measured by the above method， the occurrence of acute renal injury （AKI） was recorded and the relationship of polymyxin B concentration in plasma with AKI was analyzed. RESULTS The linear ranges of polymyxin B1 and polymyxin B2 were 200-20 000， 50-5 000 ng/mL （r＞0.995）， and the lower limits of quantification were 200 and 50 ng/mL， respectively. RSDs of intra‐day and inter‐day precision tests were not higher than 12.06%， the average extraction recovery was 103.04%-117.44%， and RSDs of matrix effect test and stability test were all not higher than 7.42%. Steady state trough and peak plasma concentration were （2.54±2.52） and （8.17±5.20） mg/L for 79 clinical patients using polymyxin B. Eighteen patients out of 27 included patients developed AKI， with an incidence of 66.67%. The peak concentration of polymyxin B of patients without AKI was significantly lower than that of patients with AKI （P＜0.05）， but there was no significant difference in the trough concentration between two groups （P＞0.05）. CONCLUSIONS The established UPLC-MS/MS has the advantages of simple operation and high sensitivity， and can be used to monitor the plasma concentration of polymyxin B in patients. The occurrence of AKI is correlated with the peak concentration of polymyxin B. |
| 期刊： | 2023年第34卷第06期 |
| 作者： | 甘雨；喻明洁；刘芳；程林；陈勇川 |
| AUTHORS： | GAN Yu，YU Mingjie，LIU Fang，CHENG Lin，CHEN Yongchuan |
| 关键字： | 多黏菌素B；超高效液相色谱-串联质谱法；血药浓度；急性肾损伤 |
| KEYWORDS： | polymyxin B； UPLC-MS/MS； plasma concentration； acute renal injury |
| 阅读数： | 961 次 |
| 本月下载数： | 14 次 |
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