Peculiarities of determination of tetraethylthiuramdisulfide (antabuse) by derivative spectrophotometry

Tetraethylthiuram disulfide or antabuse (1,1',1'',1'''-[disulfanedylbis-(carbonothioylnitrilo)]tetratane) is a biologically active substance that can be used to treat alcohol and cocaine addiction, a number of infections, cataracts, and some neurological and oncological diseases.

Objective - development of a method for determining tetraethylthiuram disulfide in a substance and a model biological object (liver tissue) using the derivative spectrophotometry method.

Materials and methods. The object of the study is tetraethylthiuram disulfide (1,1',1'',1'''-[disulfanedylbis-(carbonothioylnitrilo)]tetratane). The applied chemical-analytical method of research is second-order derivative electron spectrophotometry. Liver tissue was used as a model of a biological matrix.

Results. A method for studying biomaterial for the presence of tetraethylthiuram disulfide has been developed, based on isolation with toluene, purification by changing the solvent and sorption in a thin layer of silica gel, detection by TLC with subsequent identification and assessment of the quantitative content by spectrophotometry in the UV region based on the calculation of second-order derivatives. The position of the maxima of the pronounced and hidden absorption bands of the analyte in the electronic spectrum has been clarified. The presence of a linear dependence of the intensity of light absorption of tetraethylthiuram disulfide in the acetonitrile medium on the concentration of the analyte in the photometric solution (range 1.0-24.0 μg/ml) has been shown. It has been established that the developed method allows determining (61.42-63.11) ± (2.66-4.21)% tetraethylthiuram disulfide in model mixtures with liver tissue containing 0.005-0.2% of the analyte. The values of the standard deviation S and the relative standard deviation Sr, % are 2.14-3.39 and 3.39-5.51, respectively.

Conclusion. Using the method of derivative spectrophotometry, a reproducible and correct method for assessing the qualitative and quantitative content of tetraethylthiuram disulfide in the substance and model biomatrix (liver tissue) has been developed.

1. Lanz J., Biniaz-Harris N., Kuvaldina M., Jain S., Lewis K., Fallon B.A. Disulfiram: Mechanisms, Applications, and Challenges. Antibiotics. 2023;12:524. DOI: 10.3390/antibiotics12030524.

2. Agarwal R. Diffuse subendocardial ischemia secondary to disulfiram-alcohol ingestion. Indian J Pharmacol. 2022;54(2):146-147. DOI: 10.4103/ijp.ijp_930_21.

3. Frankl S., Hadar P.N., Yakhkind A., Lang A.E., Sandsmark D.K. Devastating Neurological Injury as a Result of Treatment of «Chronic Lyme Disease». Mayo Clin. Proc. 2021;96:2005-2007. DOI: 10.1016/j.mayocp.2021.05.011.

4. Nsairat H., Alshaer W., Lafi Z., Ahmad S., Al-Sanabrah A., El-Tanani M. Development and validation of reversed-phase-HPLC method for simultaneous quantification of fulvestrant and disulfiram in liposomes. Bioanalysis. 2023;15(23):1393-1405. DOI: 10.4155/bio-2023-0137.

5. Lanz J., Biniaz-Harris N., Kuvaldina M., Jain S., Lewis K., Fallon B.A. Disulfiram: Mechanisms, Applications, and Challenges. Antibiotics. 2023;12:524. DOI: 10.3390/antibiotics12030524.

6. Potula H-Н.S.K., Shahryari J., Inayathullah M., Malkovskiy A.V., Kim K.M., Rajadas J. Repurposing Disulfiram (Tetraethylthiuram Disulfide) as a Potential Drug Candidate against Borrelia Burgdorferi In Vitro and In Vivo. Antibiotics. 2020;9(9):633. DOI: 10.3390/antibiotics9090633.

7. Kedik S.A., Panov A.V., Tyukova V.S. Standardization of the inclusion complex of disulfiram with hydroxypropyl-β-cyclodextrin for its use as a pharmaceutical substance. Razrabotka i registraciya lekarstvennyh sredstv. 2016;(2):104-107 (in Russ.). EDN: WYJZLN.

8. Gajree N., Khan N. Methaemoglobinaemia Secondary to Disulfiram. Alcohol and Alcoholism. 2022;57(4):529. DOI: 10.1093/alcalc/agab040,

9. Jafarova S. The Role of Neurotransmitters in Protecting Brain during Acute Hypoxia. Bull Georg Natl Acad Sci. 2021;15(3):79-84.

10. Stransky G., Lambing M.K., Simmons G.T., Robinson A. Methemoglobinemia in a fatal case of disulfiram-ethanol reaction. J Anal Toxicol. 1997;21:178-179. DOI: 10.1093/jat/21.2.178.

11. Radaschin D.S., Bujoreanu F.C., Tatu A.L. Disulfiram-Induced Baboon Syndrome. Am. J. Ther. 2020;29(2):e272-e273. DOI: 10.1097/MJT.0000000000001227.

12. Heath M.J., Pachar J.V., Perez Martinez A.L., Toseland P.A. An exceptional case of lethal disulfiram-alcohol reaction. Forensic Science International. 1992;56(1):45-50. DOI: 10.1016/0379-0738(92)90145-m.

13. Shormanov V.K., Kovalenko E.A., Duritsyn E.P., Maslov S.V., Galushkin S.G., Pronichenko E.I. Determination of carbofuran in forensic chemical analysis of biological material. Sudebno-meditsinskaya ekspertiza. 2013;56(4):30-34 (in Russ.). EDN: QZXJRT.

14. Shormanov V.K., Kovalenko E.A., Duritsyn E.P. Determination of furadan in biological fluids. Sudebno-meditsinskaya ekspertiza. 2005;48(5): 36-39 (in Russ.)

15. Kvacakhia L.L., Shormanov V.K., Maksina E.V. Determination of Mexidol in tablets by derivative spectrophotometry. Humans and their health. 2023;26(2):80-85 (in Russ.). DOI: 10.21626/vestnik/2023-2/10. EDN: DHVEMI.