Determination of polymyxin B concentration in plasma and its application in critically ill patients

GAN Yu; YU Mingjie; LIU Fang; CHENG Lin; CHEN Yongchuan

doi:10.6039/j.issn.1001-0408.2023.06.12

您当前的位置：

首页 >

文章列表页 >

Determination of polymyxin B concentration in plasma and its application in critically ill patients

更新时间：2023-03-24

- Determination of polymyxin B concentration in plasma and its application in critically ill patients
- ZHONGGUO YAOFANG Vol. 34, Issue 6, Pages: 704-709(2023)
- 作者机构：
  
  陆军军医大学第一附属医院药学部，重庆　400038
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.06.12
  CLC： R978
- Published：30 March 2023，
  
  Received：25 October 2022，
  
  Revised：06 February 2023，
扫描看全文
甘雨,喻明洁,刘芳等.多黏菌素B血药浓度的测定及其在重症患者中的应用 ^Δ[J].中国药房,2023,34(06):704-709.

GAN Yu,YU Mingjie,LIU Fang,et al.Determination of polymyxin B concentration in plasma and its application in critically ill patients[J].ZHONGGUO YAOFANG,2023,34(06):704-709.
甘雨,喻明洁,刘芳等.多黏菌素B血药浓度的测定及其在重症患者中的应用 ^Δ[J].中国药房,2023,34(06):704-709. DOI： 10.6039/j.issn.1001-0408.2023.06.12.

GAN Yu,YU Mingjie,LIU Fang,et al.Determination of polymyxin B concentration in plasma and its application in critically ill patients[J].ZHONGGUO YAOFANG,2023,34(06):704-709. 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 C

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

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（

＞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（

＜0.05），但两者谷浓度比较差异无统计学意义（

＞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 C

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

603.2→101.2 （polymyxin B1），

595.7→101.1 （polymyxin B2） and

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 （

＞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 （

＜0.05）， but there was no significant difference in the trough concentration between two groups （

＞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.

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

Keywords

UPLC-MS/MSplasma concentrationacute renal injury

references

NANG S C，AZAD M A K，VELKOV T，et al. Rescuing the last-line polymyxins：achievements and challenges[J]. Pharmacol Rev，2021，73（2）：679-728.

中国医药教育协会感染疾病专业委员会，中华医学会呼吸病学分会，中华医学会重症医学分会，等. 中国多黏菌素类抗菌药物临床合理应用多学科专家共识[J]. 中华结核和呼吸杂志，2021，44（4）：292-310.

Antibiotics：Ⅵ： neomycin，polymyxin B，bacitracin and tyrothricin[J]. N Engl J Med，1958，258（24）：1213-1215.

YANG Q W，POGUE J M，LI Z K，et al. Agents of last resort：an update on polymyxin resistance[J]. Infect Dis Clin North Am，2020，34（4）：723-750.

WILLYARD C. The drug-resistant bacteria that pose the greatest health threats[J]. Nature，2017，543（7643）：15.

HU F P，GUO Y，YANG Y，et al. Resistance reported from China antimicrobial surveillance network（CHINET）in 2018[J]. Eur J Clin Microbiol Infect Dis，2019，38（12）：2275-2281.

RABANAL F，CAJAL Y. Recent advances and perspectives in the design and development of polymyxins[J]. Nat Prod Rep，2017，34（7）：886-908.

JUSTO J A，BOSSO J A. Adverse reactions associated with systemic polymyxin therapy[J]. Pharmacotherapy，2015，35（1）：28-33.

中国研究型医院学会危重医学专业委员会，中国研究型医院学会感染性疾病循证与转化专业委员会. 多黏菌素临床应用中国专家共识[J]. 中华危重病急救医学，2019，31（10）：1194-1198.

TSUJI B T，POGUE J M，ZAVASCKI A P，et al. International consensus guidelines for the optimal use of the polymyxins：endorsed by the American College of Clinical Pharmacy（ACCP），European Society of Clinical Micro-biology and Infectious Diseases（ESCMID），Infectious Di-seases Society of America（IDSA），International Society for Anti-infective Pharmacology（ISAP），Society of Critical Care Medicine（SCCM），and Society of Infectious Di-seases Pharmacists（SIDP）[J]. Pharmacotherapy，2019，39（1）：10-39.

KAUFMANN A. High-resolution mass spectrometry for bioanalytical applications：is this the new gold standard?[J]. J Mass Spectrom，2020；55（9）：e4533.

国家药典委员会.中华人民共和国药典：四部[S]. 2020年版.北京：中国医药科技出版社，2020：466-472.

Section 2：AKI definition[J]. Kidney Int Suppl（2011），2012，2（1）：19-36.

MENG M，WANG L，LIU S，et al. Simultaneous quantitation of polymyxin B1，polymyxin B2 and polymyxin B1-1 in human plasma and treated human urine using solid phase extraction and liquid chromatography-tandem mass spectrometry[J]. J Chromatogr B Analyt Technol Biomed Life Sci，2016，1012/1013：23-36.

HEE K H，LEAW Y K J，ONG J L，et al. Development and validation of liquid chromatography tandem mass spectrometry method quantitative determination of polymyxin B1，polymyxin B2，polymyxin B3 and isoleucine-polymyxin B1 in human plasma and its application in clinical studies[J]. J Pharm Biomed Anal，2017，140：91-97.

COVELLI J，RUSZAJ D，STRAUBINGER R，et al. The development and validation of a simple liquid chromatography-tandem mass spectrometry method for polymyxin B1 and B2 quantification in different matrices[J]. J Chromatogr B Analyt Technol Biomed Life Sci，2017，1065/1066：112-118.

董金材，曾鳞粞，王曦，等. 生物样品前处理技术在药动学研究中的应用进展[J]. 中药新药与临床药理，2018，29（1）：110-117.

SANDRI A M，LANDERSDORFER C B，JACOB J，et al. Population pharmacokinetics of intravenous polymyxin B in critically ill patients：implications for selection of dosage regimens[J]. Clin Infect Dis，2013，57（4）：524-531.

ZAVASCKI A P，GOLDANI L Z，CAO G Y，et al. Pharmacokinetics of intravenous polymyxin B in critically ill patients[J]. Clin Infect Dis，2008，47（10）：1298-1304.

SISAY M，HAGOS B，EDESSA D，et al. Polymyxin-induced nephrotoxicity and its predictors：a systematic review and meta-analysis of studies conducted using RIFLE criteria of acute kidney injury[J]. Pharmacol Res，2021，163：105328.

DENG Y，GU J Y，LI X，et al. Does monitoring total and free polymyxin B1 plasma concentrations predict polymyxin B-induced nephrotoxicity? A retrospective study in critically ill patients[J]. Infect Dis Ther，2022，11（4）：1591-1608.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

通过核因子E2相关因子2信号通路保护急性肾损伤的中药有效成分的研究进展

Effects of hypoalbuminemia and human albumin supplementation on patients with acute kidney injury after off-pump coronary artery bypass grafting

Related Author

王圳伊

罗佳承

阮豪南

王露露

张晶

QIU Shuijing

HU Zhansong

TU Ying

Related Institution

No data

Address：8/F,129 Daping Main Street,Yuzhong District,Chongqing 400042,P.R.China
Technical support is provided by Beijing Founder Electronics co., LTD 渝ICP备15012710号公网安备50010302001817
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰