title: Simultaneous quantification of antimicrobial agents for multidrug-resistant bacterial infections in human plasma by ultra-high-pressure liquid chromatography-tandem mass spectrometry.
abstract: Antibiotic-resistant bacterial infection is one of the most serious clinical problems worldwide. Vancomycin, teicoplanin, daptomycin, and colistin are glycopeptide and lipopeptide antibiotics that are frequently used to treat multidrug-resistant bacterial infections. Therapeutic drug monitoring is recommended to ensure both safety and efficacy and to improve clinical outcomes. This study developed a fast, simple, and sensitive ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of the concentrations of these four drugs in human plasma. The sample preparation process includes a simple protein denaturation step using acetonitrile, followed by an 11-fold dilution with 0.1% formic acid. Eight target peaks for the four drugs can be analyzed within 3 min using a Kinetex™ 2.6 μm C18 column. The mass spectrometry parameters were optimized, and two transitions for each target peak were used for multiple reaction monitoring, which provided high sensitivity and specificity. The UHPLC-MS/MS method was validated over clinical concentration ranges. The intra-day and inter-day precisions for the ratio of the peak area of each analyte to the peak area of the internal standard were all below 12.7 and 14.7% relative standard deviations, respectively. The accuracy at low, medium, and high concentrations of the eight target peaks was between 89.3 and 110.7%. The standard curves for the analytes were linear and had coefficients of determination higher than 0.997. The limits of detection were all below 70 ng mL(-1). The use of this method to analyze patient plasma samples confirmed that it is effective for the therapeutic drug monitoring of these four drugs and can be used to improve the therapeutic efficacy and safety of treatment with antibiotics.
authors.affiliation: The Metabolomics Core Laboratory, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: I-Lin
authors.initials: IL
authors.lastname: Tsai
authors.forename: Hsin-Yun
authors.initials: HY
authors.lastname: Sun
authors.forename: Guan-Yuan
authors.initials: GY
authors.lastname: Chen
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Lin
authors.forename: Ching-Hua
authors.initials: CH
authors.lastname: Kuo
mesh_terms: D000097:Acetonitriles / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000097:blood* / Q000627:therapeutic use; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003091:Colistin / Q000097:blood* / Q000627:therapeutic use; D017576:Daptomycin / Q000097:blood* / Q000627:therapeutic use; D016903:Drug Monitoring; D024901:Drug Resistance, Multiple, Bacterial; D005561:Formates / Q000737:chemistry; D016905:Gram-Negative Bacterial Infections / Q000097:blood* / Q000188:drug therapy / Q000382:microbiology; D016908:Gram-Positive Bacterial Infections / Q000097:blood* / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D057230:Limit of Detection; D011489:Protein Denaturation; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods; D017334:Teicoplanin / Q000097:blood* / Q000627:therapeutic use; D014640:Vancomycin / Q000097:blood* / Q000627:therapeutic use
chemical_list: D000097:Acetonitriles; D000900:Anti-Bacterial Agents; D005561:Formates; C030544:formic acid; D017334:Teicoplanin; D014640:Vancomycin; D017576:Daptomycin; C032159:acetonitrile; D003091:Colistin
keywords: Colistin; Daptomycin; LC–MS/MS; Teicoplanin; Vancomycin