| 2020 | Rapid and simultaneous determination of ten anti-tuberculosis drugs in human plasma by UPLC-MS/MS with applications in therapeutic drug monitoring. | J Chromatogr B Analyt Technol Biomed Life Sci | Tuberculosis remains a global challenge, particularly with a growing number of resistant cases, which may become an obstacle to eliminating this disease. Standardized short-course therapy composed of first-line anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF), ethambutol (EMB), and pyrazinamide (PZA) is playing vital roles for curbing the rapid spread of tuberculosis. However, some patients have poor responses to standardized short-course therapy. As the number of drug-resistant tuberculosis increase, some other anti-tuberculous drugs are needed to achieve better treatment outcomes. In this study, we established a UPLC-MS/MS method for simultaneous detection of ten anti-tuberculosis drugs in human plasma including INH, EMB, PZA, RIF, rifampin, rifapentine as well as four second-line antituberculosis drugs, i.e. ethionamide, Protionamide, thiosemicarbazone and clofazimine. This study contains almost all the commonly used anti-tuberculosis drugs. The plasma samples were treated with acetonitrile to precipitate proteins, and doped with the isotope internal standard. A Shiseido CAPCELL RAK-ADME (2.1 mm × 50 mm, 3 μm) column was used for chromatographic separation, and acetonitrile-water (containing 0.1% formic acid) was the mobile phase. The separation used gradient elution with a flow rate of 0.4 mL/min. The column temperature was 40 °C, and the sample volume was 1 μL. The electrospray ionization source (ESI) and the positive ion multiple reaction monitoring (MRM) mode were used for the detection. The analysis time was as short as 7 min. The results show a good linear relationship under optimized conditions in the range of 5.00-7.50 × 10, 1.00-1.50 × 10, 5.00-5.00 × 10, 5.00-7.50 × 10, 1.00-3.00 × 10, 1.00 × 10-1.00 × 10, 1.00-3.00 × 10, 1.00-3.00 × 10, 2.00-4.00 × 10, and 1.00 × 10-2.00 × 10 ng/mL for INH, EMB PZA, RIF, rifabutin, rifapentine, ethionamide, Protionamide, thiosemicarbazone, and clofazimine, respectively, with a linear correlation coefficient of R > 0.99. Finally, 34 patients with pulmonary TB were tested for therapeutic drug monitoring. The results showed that the presented method have significant advances in sensitivity, separation efficiency and simplicity. |
| 2008 | [Effects of two treatment regimens for drug-resistant tuberculosis in tuberculosis control project areas: a comparative study]. | Zhonghua Yi Xue Za Zhi | To search for an ideal therapeutic regimen for multidrug resistant tuberculosis conforming to the situation of China.One hundred and fifty-four patients with rifampin-resistant tuberculosis, 114 multi-drug resistant (MDR-TB) and 40 resistant to other drugs, in Heilongjiang, Zhejiang, and Shenzhen, 107 males and 47 females, aged 39 (19-77), were randomly divided into 2 groups: 85 patients in the group of drug-resistant regimen, 3RFT AM Ofx Pto PAS-INH/5RFT Ofx Pto PAS-INH regimen, including rifapentine (RFT), amikacin (Am), ofloxacin (Ofx), Protionamide (Pto), para-aminosalicylic acid-isoniazid (PAS-INH) for 3 months and then RFT, Ofx, Pto, and PAS-INH for 5 months, and 69 in the retreatment regimen group undergoing 3 H3R3Z3E3S3/5 H3R3E3, including isoniazid (H), rifampin (R), pyrazinamide (Z), ethambutol (E), and streptomycin (S) for 3 months and then H, R, and E for 5 months. Sputum smear was checked and the sputum smear conversion rate was calculated as an effective treatment indicator 3, 6, and 8 months later.One hundred and fourteen of the 154 patients were treated for a good 8 months. The sputum smear conversion rate 8 months after treatment of the drug-resistant regimen group was 65.9% (56/85), significantly higher than that of the retreatment regimen group [40.6% (28/69), chi2 = 9.834, P = 0.002]. Eighty-five of the 114 MDR-TB patients had been treated for a good 8 months with a sputum smear conversion rate of 61.8% (42/68), significantly higher than that of the retreatment regimen group [39.1% (18/46), chi2 = 5.638, P = 0.018]. Sputum smear conversion at the end of the 8th month was related to age, course of disease, therapeutic regimen, and the type of drug-resistance (all P < 0.05). The side-effect rate of the drug-resistant regimen group was 23.9% (17/71), higher than that of the retreatment regimen group [18.6% (8/43)], but not significantly (chi2 = 0.446, P = 0.504).The drug-resistant regimen recommended above is more effective than the retreatment regimen and should be considered in the areas where the WHO guideline fails to be followed or drug sensitivity test (DST) cannot be conducted and adjusted according to the results of DST and treatment. |