Page 74 - 《中国药房》2023年6期

·药物与临床·

多黏菌素B血药浓度的测定及其在重症患者中的应用 Δ

甘 雨 ，喻明洁，刘 芳，程 林，陈勇川（陆军军医大学第一附属医院药学部，重庆 400038）
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中图分类号 R978 文献标志码 A 文章编号 1001-0408（2023）06-0704-06
DOI 10.6039/j.issn.1001-0408.2023.06.12

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 BEH C18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0.5 mL/min，进样量为10 μL。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/z 603.2→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200～20 000、50～5 000 ng/mL（r＞0.995），
定量下限分别为 200、50 ng/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。
关键词 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

Determination of polymyxin B concentration in plasma and its application in critically ill patients
GAN Yu，YU Mingjie，LIU Fang，CHENG Lin，CHEN Yongchuan（Dept. of Pharmacy， the First Affiliated
Hospital of Army Medical University， Chongqing 400038， China）

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.
KEYWORDS polymyxin B； UPLC-MS/MS； plasma concentration； acute renal injury

Δ 基金项目 重庆市科卫联合医学科研项目（No.2019ZDXM052） 多黏菌素是多黏类芽孢杆菌发酵的一类产物，其中
＊第一作者 硕士研究生。研究方向：体内药物分析。E-mail： 多黏菌素 B 的应用较为广泛。多黏菌素 B 由 30 多种脂
276132043@qq.com
肽组成，主要成分为多黏菌素 B1 和 B2 [1―2] ，可用于耐药
# 通信作者 副主任药师，硕士生导师，硕士。研究方向：抗菌药物
[3]
临床药理学。电话：023-68754462。E-mail：zwmcyc@163.com 铜绿假单胞菌感染的临床治疗 。由于多黏菌素所致肾

· 704 · China Pharmacy 2023 Vol. 34 No. 6 中国药房 2023年第34卷第6期