Determination of Colistin and Colistimethate Levels in Human Plasma and Urine by High-Performance Liquid Chromatography-Tandem Mass Spectrometry

作者：Bihan Kevin; Lu Qin; Enjalbert Manon; Apparuit Maxime; Langeron Olivier; Rouby Jean Jacques; Funck Brentano Christian; Zahr Noel^*

来源：Therapeutic Drug Monitoring, 2016, 38(6): 796-803.

DOI：10.1097/FTD.0000000000000345

• colistin
• mass spectrometry
• pharmacokinetics
• colistimethate sodium

Background: Colistin is a polypeptide antibiotic from the polymyxin E group used for the treatment of infections caused by multidrug-resistant gram-negative bacteria. The main constituents, accounting for approximately 85% of this mixture, are colistin A (polymyxin E1) and colistin B (polymyxin E2). The aim of this study was to develop and validate new and fast methods of quantification of colistin A and B and its precursors [colistin methanesulfonate sodium (CMS) A and B] by ultraperformance liquid chromatography-tandem mass spectrometry in plasma and urine with short pretreatment and run times.
Methods: Chromatography was performed on an Acquity UPLC-MS/MS system (WATERS) with a WATERS Acquity UPLC C18 column (4.6 x 150 mm, 3.5 mm particle size). The pretreatment of samples consists of precipitation and extraction into microcolumns plate and HLB 96-well plate 30 mm-30 mg (OASIS) with a Positive Pressure-96 (WATERS).
Results: Quantification was performed using a multiple reaction monitoring of the following transitions: m/z 390.9/385.1 for colistin A, m/z 386.2/101.0 for colistin B, and m/z 602.4/241.1 for polymyxin B1 sulfate. In plasma and urine, calibration curves were linear from 30 to 6000 ng/mL for colistin A and from 15 to 3000 ng/mL for colistin B. With an acceptable accuracy and precision, the lower limit of quantification were set at 24.0 ng/mL and 12.0 ng/mL for colistin A and B in plasma, and at 18.0 ng/mL and 9.0 ng/mL for colistin A and B in urine.
Conclusions: These LC-MS/MS methods of quantification for colistin A and B and its precursors (CMS A and B) in plasma and urine are fast, simple, specific, sensitive, accurate, precise, and reliable. Furthermore, they are linear and repeatable. These procedures were successfully applied to a pharmacokinetic study of a critically ill patient suffering from ventilator-associated pneumonia, who was treated with nebulized CMS.

• 出版日期2016-12