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

Author(s):

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

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 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

Affiliation:

Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, Guilin Medical University, Guilin 541004, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508



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