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Antibiotics 2018, 7(4), 107; https://doi.org/10.3390/antibiotics7040107

Optimization and Validation of a Chromatographic Method for the Quantification of Isoniazid in Urine of Tuberculosis Patients According to the European Medicines Agency Guideline

1
Department of Chemistry, University Doctor Harisingh Gour Vishwavidyalaya (A Central University), Sagar, Madhya Pradesh 470003, India
2
Química Bioanalítica, Departament de Química Física i Analítica, Escola Superior de Tecnologia i Ciències Experimentals, Universitat Jaume I, 12071 Castelló, Spain
3
Department of Criminology and Forensic Science, Harisingh Gour Vishwavidyalaya (A Central University), Sagar, Madhya Pradesh 470003, India
*
Author to whom correspondence should be addressed.
Received: 27 November 2018 / Revised: 8 December 2018 / Accepted: 9 December 2018 / Published: 11 December 2018
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Abstract

Isoniazid is a drug that is widely used against tuberculosis. However, it shows high interpatient variability in metabolism kinetics and clinical effect, which complicates the prescription of the medication and jeopardizes the success of the therapy. Therefore, in a specific patient, the pharmacokinetics of the drug must be elucidated to decide the proper dosage and intake frequency to make the drug suitable for therapeutic drug monitoring. This can be performed by the quantification of the drug in urine as this process is non-invasive and allows the effects of long-time exposure to be inferred. The paper describes the development of a micellar liquid chromatographic method to quantify isoniazid in urine samples. Extraction steps were avoided, making the procedure easy to handle and reducing the waste of toxic organic solvents. Isoniazid was eluted in less than 5 min without interference from other compounds of the urine using a mobile phase containing 0.15 SDS–12.5% 1-propanol (v/v)–Na2HPO4 0.01 M buffered at pH 7, running at 1 mL/min under isocratic mode through a C18 column with the detection wavelength at 265 nm. The method was validated by following the requirements of the Guidelines on Bioanalytical Method Validation issued by the European Medicines Agency (EMA) in terms of selectivity, calibration curve (r2 = 0.9998 in the calibration range (0.03–10.0 μg/mL), limit of detection and quantification (10 and 30 ng/mL respectively), precision (<16.0%), accuracy (−0.9 to +8.5%), carry-over, matrix effect, and robustness. The developed method was applied to quantify isoniazid in urine samples of patients of an Indian hospital with good results. The method was found to be useful for routine analysis to check the amount of isoniazid in these patients and could be used in its therapeutic monitoring. View Full-Text
Keywords: direct injection; drug; micellar; tuberculosis; urine; validation direct injection; drug; micellar; tuberculosis; urine; validation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Mishra, P.; Albiol-Chiva, J.; Bose, D.; Durgbanshi, A.; Peris-Vicente, J.; Carda-Broch, S.; Esteve-Romero, J. Optimization and Validation of a Chromatographic Method for the Quantification of Isoniazid in Urine of Tuberculosis Patients According to the European Medicines Agency Guideline. Antibiotics 2018, 7, 107.

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