The excretion study of 4-(5-methyl-1,3,4-oxadiazole-2-yl)-benzenesulfonamide in rats

Authors

DOI:

https://doi.org/10.18413/rrpharmacology.11.524

Abstract

Introduction: The 4-(5-methyl-1,3,4-oxadiazole-2-yl)-benzenesulfonamide (ODASA) is a newcarbonic anhydrase II inhibitor for open-angle glaucoma treatment, but the excretion study of this compound has not been performed yet. Aim: Calculation of excretion parameters of ODASAand its metabolites in urine and feces in rats.

Materials and Methods: The ODASA excretion was investigated on 6 Wistar rats. The 1% suspension of ODASA was instilled into each eye in a volume of 20μL (1.6 mg/kg). Excreta were collected using metabolic cages. Sampling of feces was performed every 24 h for 384 h after the administration. Urine was taken frequently in first day of experiment: 4 h, 8 h and 12 h after administration. Samples was stabilized and frozen (temperature <-70°C). Quantification of ODASA, 4-[5-(hydroxymethyl)-1,3,4-oxadiazole-2-yl]-benzenesulfonamide (M1), N-hydroxy-4-(5-methyl-1,3,4-oxadiazole-2-yl)-benzenesulfonamide (M2), 4-(5-methyl-1,3,4-oxadiazole-2-yl)-benzenesulfonic acid (M3) was carried out by HPLC-ESI-MS/MS. M2 was unstable in samples, and its content was calculated by summing the concentrations of M2 and its degradation product M3. Kinetex Phenyl Hexyl column (50*4.6 mm, 2.6 µm) was used for chromatographic separation.

Results: The developed bioanalytical methods for rat excreta analysis were validated in the range of 10-10000 ppb for ODASA and M1, 1-1000 ppb – for M2, and 5-5000 ppb – for M3. Part of 16.29±1.60% of the active compound was eliminated in unchanged form, 80.27±1.68% – in the form of M1, and 3.43±0.33% – in form of M2 (М±SEM). The drug is mainly excreted by renal route: 14.22±1.43% in the form of ODASA, 69.90±1.80% – in the form of M1, and 1.88±0.24% – in the form of M2 (М±SEM). The highest rate of renal excretion of the studiedcompounds was observed in period of 8-12 hours after administration. The complete elimination of ODASA was achieved through 360 h after administration.

Conclusion: Most part of ODASA is eliminated in the form of M1. The main route of excretion is renal. The use of validated bioanalytical methods guaranteed reliability of the obtained data.

Graphical Abstract

Keywords:

HPLC-MS/MS, urine, feces, stabilization, validation, pharmacokinetics, excretion, rats, carbonic anhydrase II inhibitor, N-hydroxysulfonamide

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Author Contribution

Alexander L. Khokhlov, Yaroslavl State Medical University

Doctor Habil. of Medical Sciences, Professor, Member of The Russian Academy of Sciences, Head of the Department of Pharmacology and Clinical Pharmacology, rector of Yaroslavl State Medical University, Yaroslavl, Russia; e-mail: al460935@yandex.ru; ORCID ID:https://orcid.org/0000-0002-0032-0341. The author’s contribution: formulation and development of the aim and objectives; analysis and interpretation of the obtained data; critical review of the draft copy and provision of valuable comments.

Ilya I. Yaichkov, Yaroslavl State Pedagogical University named after K.D. Ushinsky

Candidate of Pharmaceutical Sciences, research fellow of the Department of Analytical Development and Quality Control of M.V. Dorogov Pharmaceutical Technology Transfer Center of Yaroslavl State Pedagogical University named after K.D. Ushinsky; research fellow of the Institute of Pharmacy of Yaroslavl State Medical University, Yaroslavl, Russia; e-mail: i.yaichkov@yspu.org; ORCID ID: https://orcid.org/0000-0002-0066-7388. The author’s contribution: concept development; development of design of pharmacokinetic study; development of bioanalytical methods; analysis of samples; analysis and interpretation of the obtained data; writing the bioanalytical part and editing the manuscript.

Anton A. Shetnev, Yaroslavl State Pedagogical University named after K.D. Ushinsky

Candidate of Chemical Sciences, Head of the Department of Pharmaceutical Development of V. Dorogov Pharmaceutical Technology Transfer Center of Yaroslavl State PedagogicalUniversity named after K.D. Ushinsky, Yaroslavl, Russia; e-mail: a.shetnev@list.ru; ORCID ID: https://orcid.org/0000-0002-4389-461X. The author’s contribution: synthesis of substances of the drug and its metabolite.

Mikhail K. Korsakov, Yaroslavl State Pedagogical University named after K.D. Ushinsky

Doctor Habil. of Chemical Sciences, Professor of the Department of Chemistry, Theory and Methods of Teaching Chemistry, Head of The Center of Transfer of Pharmaceutical Technology named after M.V. Dorogov of Yaroslavl State Pedagogical University named after K.D. Ushinsky, Yaroslavl, Russia; e-mail: korsakov@yspu.org; ORCID ID: https://orcid.org/0000-0003-0913-2571. The author’s contribution: formulation and development of the aim and objectives; analysis and interpretation of the obtained data; critical review of the draft copy and provision of valuable comments.

Nikita N. Volkhin , Yaroslavl State Pedagogical University named after K.D. Ushinsky

Assistant lecturer of the Department of Pharmacology and Clinical Pharmacology of Yaroslavl State Medical University; junior research fellow of the Department of Pharmacological Studies of V. Dorogov Pharmaceutical Technology Transfer Center of Yaroslavl State Pedagogical University named after K.D. Ushinsky, Yaroslavl, Russia; e-mail: nnvolkhin@ysmu.ru; ORCID ID: https://orcid.org/0000-0002-4275-9037. The author’s contribution: working with laboratory animals; blood and plasma sample collection.

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Published

25-12-2025

How to Cite

Khokhlov AL, Yaichkov II, Shetnev AA, Korsakov MK, Volkhin NN (2025) The excretion study of 4-(5-methyl-1,3,4-oxadiazole-2-yl)-benzenesulfonamide in rats. Research Results in Pharmacology 11(4): 187–198. https://doi.org/10.18413/rrpharmacology.11.524

Issue

Vol. 11 No. 4 (2025)

Section

Experimental Pharmacology

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Copyright (c) 2025 Khokhlov AL, Yaichkov II, Shetnev AA, Korsakov MK, Volkhin NN

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