Simultaneously Determining Seven Second-Line Anti-TB Drugs by UHPLC-
MS: Application for TDM in HIV-TB Patients

Lin       Yin; Yaru       Xing; Xiaoqin       Le; Jun       Chen; Lin       Zhang; Xiaofang       Jia; Tao       Sun; Yingying       Li; Hongzhou       Lu; Lijun       Zhang

doi:10.2174/1573412918666211123112915

Abstract

Background: To optimize therapy for patients with human immunodeficiency virus-tuberculosis (HIV-TB) coinfection, we developed an ultra-high-performance liquid chromatography/- tandem mass spectrometry (UHPLC-MS) method to monitor seven second-line anti-tuberculosis drugs.

Methods: Blood samples (n = 70) were collected from 35 patients with HIV-TB coinfection; the plasma sample was protein-precipitated and diluted with a solution containing heptafluorobutyric acid. The plasma concentrations of rifabutin (RBT), clofazimine (CLO), moxifloxacin (MFX), prothionamide (PTH), levofloxacin (LFX), amikacin (AMK), and para-aminosalicylic acid (PAS) were detected by UHPLC-MS/MS method.

Results: In these 70 samples, the mean concentrations of RBT, CLO, MFX, PTH, LFX, and AMK were 173.8 (10.0–550.0), 61.1 (54.4–67.7), 646.6 (25.0–2480.0), 120.5 (50.0–597.0), 1565.9 (100.0–3480.0), and 10753.0 (400.0–76 700.0) μg/L, respectively. Only one sample was detected to have PAS with a concentration less than the lower limit of quantification. Most of the drug concentrations detected in these patients were lower than the targeted concentrations in TB patients.

Conclusion: We created a simple UHPLC-MS method for simultaneously quantifying anti-TB drugs. The plasma concentrations in HIV-TB co-infected patients were lower than the targeted concentrations. It is important to monitor anti-TB drugs in the future. This method will facilitate the monitoring of anti-TB drugs in the future.

Keywords: UHPLC-MS/MS, second-line anti-TB drugs, HIV-TB coinfection, drug-resistant tuberculosis, therapeutic drug monitoring, plasma.

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DOI https://dx.doi.org/10.2174/1573412918666211123112915	Print ISSN 1573-4129
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Simultaneously Determining Seven Second-Line Anti-TB Drugs by UHPLC- MS: Application for TDM in HIV-TB Patients

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