title: Development and validation of a UHPLC-MS/MS assay for colistin methanesulphonate (CMS) and colistin in human plasma and urine using weak-cation exchange solid-phase extraction.
abstract: A rapid ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay method was developed for determination of CMS and formed colistin in human plasma and urine. After extraction on a 96-well SPE Supra-Clean Weak Cation Exchange (WCX) plate, the eluents were mixed and injected into the UHPLC-MS/MS system directly. A Phonomenex Kinetex XB-C18 analytical column was employed with a mobile phase consisting of solution "A" (acetonitrile:methanol, 1:1, v/v) and solution "B" (0.1% formic acid in water, v/v). The flow rate was 0.4 mL/min with gradient elution over 3.5 min. Ions were detected in ESI positive ion mode and the precursor-product ion pairs were m/z 390.7/101.3 for colistin A, m/z 386.0/101.2 for colistin B, and m/z 402.3/101.2 for polymyxin B1 (IS), respectively. The lower limit of quantification (LLOQ) was 0.0130 and 0.0251 mg/L for colistin A and colistin B in both plasma and urine with accuracy (relative error, %) <± 12.6% and precision (relative standard deviation, %) <± 10.8%. Stability of CMS was demonstrated in biological samples before and during sample treatment, and in the extract. This new analytical method provides high-throughput treatment and optimized quantification of CMS and colistin, which offers a highly efficient tool for the analysis of a large number of clinical samples as well as routine therapeutic drug monitoring.
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University & Key Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family Planning Commission, Shanghai, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University & Key Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family Planning Commission, Shanghai, China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Wu
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University & Key Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family Planning Commission, Shanghai, China.
authors.forename: Ya-Xin
authors.initials: YX
authors.lastname: Fan
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University & Key Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family Planning Commission, Shanghai, China.
authors.forename: Bei-Ning
authors.initials: BN
authors.lastname: Guo
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University & Key Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family Planning Commission, Shanghai, China. Electronic address: zhangj_fudan@aliyun.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D002411:Cation Exchange Resins; D002853:Chromatography, Liquid; D003091:Colistin / Q000032:analysis* / Q000097:blood / Q000652:urine; D006801:Humans; D057230:Limit of Detection; D052616:Solid Phase Extraction / Q000379:methods*; D053719:Tandem Mass Spectrometry
chemical_list: D002411:Cation Exchange Resins; D003091:Colistin
keywords: CMS; Colistin; Liquid chromatography–mass spectrometry; Plasma; Urine