Simultaneous determination of first-line anti-tuberculosis drugs and one metabolite of isoniazid by liquid chromatography/tandem mass spectrometry in patients with human immunodeficiency virus-tuberculosis coinfection

• DOI: 10.1016/j.heliyon.2021.e07532
• Publication Date: 2021-07-09T16:34:01Z
• Authors: Yaru Xing; Lin Yin; Xiaoqin Le; Jun Chen; Lin Zhang; Yingying Li; Hongzhou Lu; Lijun Zhang
• Keywords: Pyrazinamide; Protein precipitation

The incidence rate of tuberculosis (TB) in patients with human immunodeficiency virus (HIV) infection is 26 times higher than that other patients. Patients both infections require long-term combination therapy, which increases therapy complexity and might lead to serious adverse reactions drug-drug interactions. To optimize for HIV TB coinfection, we developed an ultra-high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) method simultaneously quantify four anti-tuberculosis drugs one isoniazid (INH) metabolite. Blood samples (n = 32) from 16 coinfection were collected. Plasma protein precipitation acetonitrile was followed by a hydrazine reaction between INH cinnamaldehyde (CA) produce phenylhydrazone (CA-INH) dilution heptafluorobutyric acid. separation performed on Acquity UHPLC HSS T3 1.8 μm column (2.1 × 100 mm, Waters) mobile phase consisting 10 mmol/L ammonium formate (pH 4) water (solvent A) 0.1 % formic acid methanol B) gradient elution. compounds detected using positive multiple monitoring model. INH, acetyl-INH (AC-INH), rifampicin (RIF), ethambutol (EMB), pyrazinamide (PZA) showed good linear relationships their quantitative ranges, lower limits quantification 48, 192, 200, 96, 480 ng/mL, respectively. inter- intraday precision within 15 %, the accuracy 85 115 %. mean plasma concentrations AC-INH, RIF, EMB, PZA 1990.23 (24–16 600), 863.06 (96–2880), 3507.05 (229–9800), 808.10 (149–2130), 18 838.33 (240–34 800) targeted HIV-negative In summary, simple UHPLC-MS/MS simultaneous first-line drugs, successfully applied it therapeutic drug coinfection. This will facilitate future.