Exploration of LC-MS/MS Method for Therapeutic Drug Monitoring and Clinical Application of Polymyxin B
DENG Yang1,2,3, XU Bing1,2,3, LI Xin1,2,3*, GUO Si-wei1,2,3, Luo Xi-lin1,2,3, LI You1,2,3
1. Department of Pharmacy, The Third Hospital of Changsha, Changsha 410015, China; 2. The Clinical Application Research Institute of Antibiotics in Changsha, Changsha 410015, China; 3. Changsha Hospital, Hunan University of Chinese Midecine, Changsha 410015, China
Abstract：OBJECTIVE To establish an LC-MS/MS method for the determination of polymyxin B (PMB1 and PMB2) concentration in human plasma and build clinical sampling process based on its stability study. METHODS Protein in plasma was precipitated by acetonitrile(containing 6.67% formic acid), and supernatant was taken and diluted with water. Chromatographic separation was achieved on a Shim-pack GIST C18(2.1 mm×100 mm,3 μm)by gradient elution with 0.1% formic acid-water and acetonitrile. Flow rate was set at 0.8 mL·min-1, and column temperature at 40 ℃. The stability of whole blood samples of PMB1 and PMB2 at different temperatures and under different conditions was investigated. RESULTS The linear ranges of PMB1 and PMB2 were good at (0.033-18.816) and (0.034-19.872) μg·mL-1 (r=0.999 9), and the lower limit concentration were 0.033 and 0.034 μg·mL-1,respectively. The extraction recoveries of low, medium and high concentration were 97.2%-110.6%, the relative standard deviation of intra-day precision and inter-day precision were less than 8.2%. With EDTA-K2 tubes as the optimal clinical blood collection, PMB1 and PMB2 in EDTA-K2 tubes and heparin sodium tubes were stable at room temperature for 10 h. Plasma samples could maintain stable at room temperature for 22 h, long-term of frozen samples after 115 days of storage and in two freeze-thaw cycle at -40 ℃, respectively. CONCLUSION The established TDM clinical sampling process fully consider the actual situation of clinical sampling for ensuring the stability of PMB and the accuracy of analysis results, which could satify the needs of clinical blood drug concentration determination.
邓阳, 徐兵, 李昕, 郭思维, 罗细林, 李尤. 多黏菌素B治疗药物监测LC-MS/MS方法探索及临床初步应用[J]. 中国药学杂志, 2021, 56(15): 1249-1254.
DENG Yang, XU Bing, LI Xin, GUO Si-wei, Luo Xi-lin, LI You. Exploration of LC-MS/MS Method for Therapeutic Drug Monitoring and Clinical Application of Polymyxin B. Chinese Pharmaceutical Journal, 2021, 56(15): 1249-1254.
SANDRI A M, LANDERSDORFER C B, JACOB J, et al. Population Pharmacokinetics of intravenous polymyxinB in critically Ⅲ patients: implications for selection of dosage regimens [J]. Clin Infect Dis, 2013, 57(4): 524-531.
THOMAS T A, BROUN E C, ABILDSKOV K M, et al. High performance liquid chromatography-mass spectrometry assay for polymyxin B1 and B2 in human plasma [J]. Ther Drug Monit, 2012, 34(4): 398-405.
ZHANG H Z, QIN F, LIU H. Identification of unknown impurities in polymyxin B sulfate by HPLC-MS/MS[J]. Chin Pharm J(中国药学杂志), 2018, 53(11):918-924.
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 Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP) [J]. Pharmacotherapy, 2019, 39(1):10-39.
CAI Y, LEE W, KWA A L. Polymyxin B versus colistin: an update [J]. Expert Rev Anti-Infe, 2015, 13(12):1481-1497.
ISMAIL B, SHAFEI M N, HARUN A, et al. Predictors of polymyxin B treatment failure in Gram-negative healthcare-associated infections among critically ill patients [J]. J Microbiol Immunol Infect, 2018, 51(6):763-769.
KANG J W, VAN SCHEPDAEL A, ORWA J A, et al. Analysis of polymyxin B sulfate by capillary zone electrophoresis with cyclodextrin as additive [J]. J Chromatogr A, 2000, 879(2):211-218.
HOWLETT M R, SELZER G B. The identification of colistin and polymyxin B by thin-layer chromatography[J]. J Chromatogr, 1967, 30(2): 630-631.
CAO G, ALI F E, CHIU F. Development and validation of a reversed-phase high-performanceliquid chromatography assay for polymyxin B in human plasma [J]. J Antimicrob Chemother, 2008, 62(5):1009-1014.
CHENG C, LIU S, XIAO D, et al. LC-MS/MS method development and validation for the determination of polymyxins and vancomycin in rat plasma [J]. J Chromatogr B(Analyt Technol Biomed Life Sci), 2010, 878(28):2831-2838.
HE J, GAO S, HU M, et al. A validated ultra-performance liquid chromatography-tandem mass spectrometry method for the quantification of polymyxin B in mouse serum and epithelial lining fluid: application to pharmacokinetic studies [J]. J Antimicrob Chemother, 2013, 68(5):1104-1110.
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.
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.
DENG Y, XU B, LI X, et al. Establishing the clinical sampling process of therapeutic drug monitoring based on stability of imipenem[J]. Chin J Clin Pharmacol (中国临床药理学杂志), 2018, 34(18): 2207-2210.
DENG Y, XU B, LI X, et al. Exploration of HPLC method for therapeutic drug monitoring of meropenem and its establishment of clinical sampling procedure [J]. Chin J Hosp Pharm (中国医院药学杂志), 2020, 40(12):1334-1338.
ZAVASCKI A P, GOLDANI L Z, CAO G, et al. Pharmacokinetics of intravenous polymyxin B in critically ill patients [J]. Clin Infect Dis, 2008, 47(10):1298-1304.