Simultaneous quantification of antimicrobial agents for multidrug-resistant bacterial infections in human plasma by ultra-high-pressure liquid chromatography-tandem mass spectrometry

I. Lin Tsai, Hsin Yun Sun, Guan Yuan Chen, Shu Wen Lin, Ching Hua Kuo

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)593-603
Number of pages11
JournalTalanta
Volume116
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

High pressure liquid chromatography
Plasma (human)
Tandem Mass Spectrometry
Anti-Infective Agents
Bacterial Infections
Mass spectrometry
formic acid
Drug Monitoring
High Pressure Liquid Chromatography
Anti-Bacterial Agents
Pharmaceutical Preparations
Daptomycin
Lipopeptides
Protein Denaturation
Colistin
Safety
Teicoplanin
Glycopeptides
Vancomycin
Monitoring

Keywords

  • Colistin
  • Daptomycin
  • LC-MS/MS
  • Teicoplanin
  • Vancomycin

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Simultaneous quantification of antimicrobial agents for multidrug-resistant bacterial infections in human plasma by ultra-high-pressure liquid chromatography-tandem mass spectrometry. / Tsai, I. Lin; Sun, Hsin Yun; Chen, Guan Yuan; Lin, Shu Wen; Kuo, Ching Hua.

In: Talanta, Vol. 116, 2013, p. 593-603.

Research output: Contribution to journalArticle

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