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Development and validation of a hydrophilic interaction liquid chromatography–tandem mass spectrometry method for the simultaneous determination of five first-line antituberculosis drugs in plasma

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Abstract

A new, sensitive and fast method for the simultaneous determination of pyrazinamide, isoniazid, streptomycin, ethambutol, and rifampicin in human plasma was developed and validated. The method required only 100 μL of plasma and one step for sample preparation by protein precipitation. The drugs were separated by using a hydrophilic interaction liquid chromatography (HILIC) column. The mobile phase was methanol and water (0.1 % formic acid and 5 mM ammonium acetate, pH 3.0 ± 0.1) in a ratio of 65:35 (v/v), which was eluted at an isocratic flow rate of 0.5 mL/min. Tandem mass spectrometry was performed with a triple-quadrupole tandem mass spectrometer. By use of the HILIC column, the detection was free of ion-pair reagents in the mobile phase, with no significant matrix effects. The total run time was less than 2 min for each sample. The method was validated by evaluating its selectivity, sensitivity, linearity, accuracy, and precision according to US Food and Drug Administration guidelines. The lower limit of quantification was 4.0 ng/mL for pyrazinamide, isoniazid, and rifampicin, 0.5 ng/mL for ethambutol, and 10.0 ng/mL for streptomycin. The intraday precision and interday precision were less than 9 %, with the accuracy ranging between −9.3 and 7.3 %. The method was successfully applied to therapeutic drug monitoring of 33 patients with tuberculosis after administration of standard antituberculosis drugs. The method has been proved to meet the high-throughput requirements in therapeutic drug monitoring.

Scatter plots of 2-h plasma drug concentration of patients after receiving a standard medication. (The lower line and the upper line represent the low and high levels of the expected plasma concentrations of the antituberculosis drugs in tuberculosis patients. Open triangles female, age 0–20 years; closed triangles male, age 0–20 years; open diamonds female, age 21–40 years; closed diamonds male, age 21–40 years; open squares female, age 41–60 years; closed squares male, age 41–60; open circles female, age 61–80 years; closed circles male, age 61–80 years)

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Acknowledgments

This work was financially supported by grants from the National Basic Research Program of China (no. 2012CB518200 and no. 30971193) and the School of Public Health and Tropical Medicine, Southern Medical University, China (no. GW201118).

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Authors and Affiliations

  1. Department of Health Inspection and Quarantine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, 510515, China

    Zhifeng Zhou & Ande Ma

  2. Department of Epidemiology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, 510515, China

    Xianbo Wu

  3. Department of Toxicology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, 510515, China

    Qinzhi Wei & Yungang Liu

  4. Department of Orthopedic and Spinal Surgery, Nan Fang Hospital, Southern Medical University, Guangzhou, 510515, China

    Peng Liu

  5. Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, North 1838th Guangzhou Avenue, Guangzhou, 510515, China

    Fei Zou

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  1. Zhifeng Zhou
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Correspondence to Fei Zou.

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Zhifeng Zhou and Xianbo Wu contributed equally to this work.

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Zhou, Z., Wu, X., Wei, Q. et al. Development and validation of a hydrophilic interaction liquid chromatography–tandem mass spectrometry method for the simultaneous determination of five first-line antituberculosis drugs in plasma. Anal Bioanal Chem 405, 6323–6335 (2013). https://doi.org/10.1007/s00216-013-7049-0

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  • DOI: https://doi.org/10.1007/s00216-013-7049-0

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