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The underlying cause of tuberculosis (TB) treatment failure is still largely unknown. A 1 H NMR approach was applied to identify and quantify a subset of TB drugs and drug metabolites: ethambutol (EMB), acetyl isoniazid (AcINH), isonicotinic acid, pyrazinamide (PZA), pyrazinoic acid and 5-hydroxy-pyrazinoic acid, from the urine of TB patients. Samples were collected before, during (weeks one, two and four) and after standardised TB treatment. The median concentrations of the EMB and PZA metabolites were comparable between the samples from patients with eventually cured and failed treatment outcomes. The INH metabolites showed comparatively elevated concentrations in the treatment failure patients during and after treatment. Variation in INH metabolite concentrations couldn't be associated with the varying acetylator genotypes, and it is therefore suggested that treatment failure is influenced more so by other conditions, such as environmental factors, or individual variation in other INH metabolic pathways., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A simple and sensitive UPLC-MS/MS assay was developed and validated for rapid determination of thiosemicarbazide derivative of isoniazid (TSC-INH), a potent anti-candidal agent in rat plasma, tissues, urine and feces. All biological samples were prepared by protein precipitation method using celecoxib as an internal standard (IS). Chromatographic separation was achieved on Acquity BEH™ C18 (50×2.1 mm, 1.7 μm) column using gradient mobile phase of acetonitrile and water (containing 0.1% formic acid) at flow rate of 0.3 mL/min. The MRM transitions were monitored at m/z 305.00→135.89 for TSC-INH and m/z 380.08→316.03 for IS in ESI negative mode. All validation parameter results were within the acceptable range described in guideline for bioanalytical method validation. The pharmacokinetic study showed that the compound TSC-INH was orally active with 66% absolute bioavailability in rats. It was rapidly absorbed with peak plasma concentration of 1985.92 ng/mL achieved within 1 h after single oral dose (10 mg/kg) administration. TSC-INH exhibited rapid distribution across the body with highest levels in liver and lungs. Penetration in brain tissues suggests that TSC-INH crossed the blood brain barrier. Only 5.23% of the orally administered drug was excreted as unconverted form in urine and feces implying that TSC-INH was metabolized extensively before excretion. With the preliminary knowledge of in vivo pharmacokinetics and disposition properties, this study will be beneficial for further development of compound TSC-INH in future studies., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Isoniazid, pyridine-4-carboxylic acid hydrazide, is an antituberculosis-agent, which is used to prevent the development of clinical tuberculosis. A validated square-wave adsorptive cathodic stripping voltammetric procedure for the trace determination of the bulk drug at the hanging mercury drop electrode (HMDE) has been developed. Under the optimized conditions, (accumulation potential=-0.9 V, accumulation time=50-300 s, scan increment=8 mV, pulse-amplitude=25 mV, frequency=120 Hz and acetate buffer at pH 5.5) isoniazed generated two irreversible cathodic peaks. The first peak current showed a linear dependence with the drug concentration over the range 5 x 10(-10)-21 x 0(-6) M. The mean percentage recoveries, based on the average of five replicate measurements, for 7 x 10(-9) and 5 x 10(-8) M isoniazid were 97.71+/-2.93 and 99.76+/-0.77, respectively. The achieved limits of detection (LOD) and quantitation (LOQ) were 1.18 x 10(-10) and 3.93 x 10(-10) M isoniazid, respectively. The procedure was applied to the assay of the drug in tablets (Isocid and T.B. Zide), spiked human serum and urine with mean percentage recoveries of 97.81+/-1.49, 97.45+/-2.09, and 97.08+/-1.06, respectively. The limits of detection of 1.47 x 10(-9) and 2.4 x 10(-8) M, and quantitation of 4.9 x 10(-9) and 8 x 10(-8) M drug in human serum and urine, respectively, were achieved. The mean values of the various pharmackinetic parameters of isoniazid (C(max), T(max), t(1/2), AUC, and K(e)), estimated from analysis of plasma of two volunteers by means of the proposed procedure were similar to literature values.

Separation and determination of capreomycin (Cp), ofloxacin (Oflx) and pasiniazide (Ipa) in urine by high-performance capillary electrophoresis (HPCE) with 280 nm detection have been studied systematically. The calibration lines were linear in the range of 0.5 approximately 50 mg 1(-1), and the detection limits (S/N = 3) were 0.15, 0.20 and 0.10 mg 1(-1) for Cp, Oflx and Ipa, respectively. The recoveries for these materials from urine were higher than 93.5%. The accuracy and intra- and inter- day reproducibility of Cp, Oflx and Ipa were determined with satisfactory results. This method was successfully used for determining Cp. Oflx and Ipa in human urine.