RESIDUAL TOXICITY VERSUS ARTEMIA SALINA OF EXPIRED AMIKACINS
DOI:
https://doi.org/10.22159/ijap.2026v18i3.51351Keywords:
Amikacin, Artemia salina bioassay, Environmental toxicology, EcopharmacovigilanceAbstract
Objetive: Amikacin is an aminoglycoside antibiotic characterized by high water solubility and environmental stability. Improper disposal of expired formulations can contribute to the spread of antibiotic resistance and disturb aquatic ecosystems. This study aimed to evaluate the residual toxicity of expired amikacin using the Artemia salina lethality bioassay.
Methods: The median lethal concentration (LC₅₀) of 39 expired and 3 non-expired amikacin vials was determined using the Artemia salina bioassay. Residual amikacin concentrations were quantified via a validated ninhydrin-based spectrophotometric method. Corrected LC₅₀ (LC₅₀C) values were calculated based on the residual concentration to assess the toxicity of degradation products.
Results: LC₅₀ values of expired samples ranged from approximately 100 to 600 mg/L, showing an inverse linear relationship with the residual concentration of the active ingredient (y = –0.0867x + 112.41; R² = 0.9249). LC₅₀ increased proportionally with time elapsed after expiration, indicating that toxicity decreases as amikacin degrades. When corrected for residual concentration, the adjusted LC₅₀ values (LC₅₀C) indicated that drug decomposition did not generate additional toxic compounds, as lethality corresponded to the remaining active ingredient.
Conclusion: These findings highlight the importance of ecopharmacovigilance and underscore the need for proper management of expired pharmaceuticals to prevent environmental contamination.
References
1. Vaikose EN, Origbo SO, Ere D, Prosper O. Comparative application of biological and ninhydrin-derivatized spectrophotometric assays in the evaluation and validation of amikacin sulfate injection. Braz J Pharm Sci. 2022;58:e201185. doi:10.1590/s2175-97902022e201185
2. Antonio DC, Minguillón-Llombart C, Joglar-Tamargo J. Química farmacéutica. 2nd ed. Madrid: Ed. Díaz de Santos; 2003.
3. Mella S, Sepúlveda M, González G, Domínguez M, Zemelman R, Ramírez C. Aminoglucósidos-aminociclitoles: características estructurales y nuevos aspectos sobre su resistencia. Rev Chil Infectol. 2004;21(4):330-338.
4. Ochoa-Retes JA, Martínez-Félix NS, Peraza-Garay FDJ, Dela Mora-Fernández AR. Frecuencia de ototoxicidad al uso de aminoglucósidos en el tratamiento de sepsis neonatal. Rev Med Univ Auton Sinaloa. 2022;10(4):192-201.
5. Sari SP, Sartika SS, Rianti A. Side effects monitoring of aminoglycoside antibiotic in hospitalized patients. Int J Appl Pharm. 2018;10(1):291-293. doi:10.22159/ijap.2018.v10s1.64
6. Langbehn RK, Michels C, Soares HM. Antibiotics in wastewater: From occurrence to biological removal by environmentally conscious technologies. Environ Pollut. 2021;275:116603. doi:10.1016/j.envpol.2021.116603
7. Huang A, Yan M, Lin J, Xu L, Gong H. A review of processes for removing antibiotics from breeding wastewater. Int J Environ Res Public Health. 2021;18(9):4909. doi:10.3390/ijerph18094909
8. Agboola TD, Nmema EE, Odetoyin BW. Distribution and antibiogram of Vibrio species from hospital wastewater in Southwest Nigeria. Pan Afr Med J. 2023;45:80. doi:10.11604/pamj.2023.45.80.35773
9. Piva S, Giacometti F, Marti E, Massella E, Cabbri R, Galuppi R, Serraino A. Could honey bees signal the spread of antimicrobial resistance in the environment? Lett Appl Microbiol. 2020;70(5):349-355. doi:10.1111/lam.13288
10. Phares CA, Danquah A, Atiah K, Agyei FK, Michael OT. Antibiotics utilization and farmers' knowledge of its effects on soil ecosystem in the coastal drylands of Ghana. PLoS One. 2020;15(2):e0228777. doi:10.1371/journal.pone.0228777
11. Tappatá LL, Tomas AL, Prieto L, Pfeiffer C, Gallaro MF, Sofio MP, Maurizi D. Insuficiencia renal aguda en pacientes tratados con aminoglucósidos. Actual Sida Infectol. 2020;28(102):13-19.
12. Chávez-Vela NA, Jáuregui-Rincón J, Araiza-Arvilla J, Montañez-Flores AL. Detección de antibióticos aminoglucósidos en plantas de tratamiento de aguas residuales mediante Dot blot. Cienc Transdisciplinar Nueva Era. 2022:207-214.
13. Molina J, Cordero E, Palomino J, Pachón J. Aminoglucósidos y polimixinas. Enferm Infecc Microbiol Clin. 2009;27(3):178-188.
14. Nian Q, Yang H, Meng E, Wang C, Xu Q, Zhang Q. Efficient adsorptive removal of aminoglycoside antibiotics from environmental water. Chemosphere. 2023;337:139379. doi:10.1016/j.chemosphere.2023.139379
15. Li R, Zhao C, Yao B, Li D, Yan S, O'Shea KE, Song W. Photochemical transformation of aminoglycoside antibiotics in simulated natural waters. Environ Sci Technol. 2016;50(6):2921-2930. doi:10.1021/acs.est.5b05234
16. Sánchez L, Neira A. Bioensayo general de letalidad en Artemia salina a las fracciones del extracto etanólico de Psidium guajava y Psidium guineense. Cult Cient. 2005;3:40-45.
17. Felis E, Kalka J, Sochacki A, Kowalska K, Bajkacz S, Harnisz M, Korzeniewska E. Antimicrobial pharmaceuticals in the aquatic environment: occurrence and environmental implications. Eur J Pharmacol. 2020;866:172813. doi:10.1016/j.ejphar.2019.172813
18. Kimera ZI, Mshana SE, Rweyemamu MM, Mboera LEG, Matee MIN. Antimicrobial use and resistance in food-producing animals and the environment: an African perspective. Antimicrob Resist Infect Control. 2020;9(1):37.
doi:10.1186/s13756-020-0697-x
19. Velo G, Moretti U. Ecopharmacovigilance for better health. Drug Saf. 2010;33(11):963-968. doi:10.2165/11539380-000000000-00000
20. Li S, Wen J, He B, Wang J, Hu X, Liu J. Occurrence of caffeine in the freshwater environment: implications for ecopharmacovigilance. Environ Pollut. 2020;263:114371. doi:10.1016/j.envpol.2020.114371
21. Wang J, He B, Yan D, Hu X. Implementing ecopharmacovigilance from a pharmacy perspective: a focus on nonsteroidal anti-inflammatory drugs. Sci Total Environ. 2017;603-604:772-784. doi:10.1016/j.scitotenv.2017.02.209
22. Zhang J, Chang VW, Giannis A, Wang JY. Removal of cytostatic drugs from aquatic environment: a review. Sci Total Environ. 2013;445-446:281-298.
doi:10.1016/j.scitotenv.2012.12.061
23. Kumarage PM, De Silva LADS, Heo GJ. Aquatic environments: a potential source of antimicrobial-resistant Vibrio spp. J Appl Microbiol. 2022;133(4):22672279. doi:10.1111/jam.15702
24. Yu B, Song N, Hu H, Chen G, Shen Y, Cong HA. Degradable triple temperature, pH-, and redox-responsive drug system for cancer chemotherapy. J Biomed Mater Res A. 2018;106(12):3203-3210. doi:10.1002/jbm.a.36515
25. Del Turco S, Basta G. Can dietary polyphenols prevent the formation of toxic compounds from Maillard reaction? Curr Drug Metab. 2016;17(6):598-607. doi:10.2174/1389200217666160308130906
26. Klelemen H, Hancu G, Kacsó E, Papp LA. Photosensitivity reactions induced by photochemical degradation of drugs. Adv Pharm Bull. 2022;12(1):77-85. doi:10.34172/apb.2022.010
27. Manocha S, Suranagi UD, Sah RK, Chandane RD, Kulhare S, Goyal N, Tanwar K. Current disposal practices of unused and expired medicines among general public in Delhi and NCR, India. Curr Drug Saf. 2020;15(1):13-19. doi:10.2174/1574886314666191008095344
28. Hu J, Quan Y, Lai Y, Zheng Z, Hu Z, Wang X, et al. A smart aminoglycoside hydrogel with tunable degradation, on-demand drug release, and high antibacterial activity. J Control Release. 2017;247:145-152. doi:10.1016/j.jconrel.2017.01.003
29. Park S, Choi K. Hazard assessment of commonly used agricultural antibiotics on aquatic ecosystems. Ecotoxicology. 2008;17(6):526-538. doi:10.1007/s10646008-0211-5
30. González-Pleiter M, Gonzalo S, Rodea-Palomares I, Leganés F, Rosal R, Boltes K, et al. Toxicity of five antibiotics and their mixtures towards photosynthetic aquatic organisms: Implications for environmental risk assessment. Water Res. 2013;47(6):2050-2064. doi:10.1016/j.watres.2013.01.020
31. Sharma VK, Johnson N, Cizmas L, McDonald TJ, Kim H. A review of the influence of treatment strategies on antibiotic resistant bacteria and antibiotic resistance genes. Chemosphere. 2016;150:702-714. doi:10.1016/j.chemosphere.2015.12.084
32. Salameh A, Alawi M, Al-Hamad A. Development and validation of an SPE-LCMS/MS method for the determination of 12 aminoglycoside antibiotics in environmental water samples. Microchem J. 2022;181:107721. doi:10.1016/j.microc.2022.107721
33. Hernández F, Ibáñez M, Bade R, Bijlsma L, Sancho JV. Investigation of pharmaceuticals and illicit drugs in waters by liquid chromatography-highresolution mass spectrometry. TrAC - Trends Anal Chem. 2014;63:140-157. doi:10.1016/j.trac.2014.08.003
34. Zhou W, Guo W, Xu W, Yang T, Li P, Luo X, et al. Highly selective detection of neomycin in contaminated water by using a fluorescent sensor array. Sens Actuators B Chem. 2021;344:130289. doi:10.1016/j.snb.2021.130289
35. Ntungwe NE, Domínguez-Martín EM, Roberto A, Tavares J, Isca VMS, Pereira P, et al. Artemia species: an important tool to screen general toxicity samples. Curr Pharm Des. 2020;26(24):2892-2908.
doi:10.2174/1381612826666200406083035
36. Nunes BS, Carvalho FD, Guilhermino LM, Van Stappen G. Use of the genus Artemia in ecotoxicity testing. Environ Pollut. 2006;144(2):453-462. doi:10.1016/j.envpol.2005.12.037
37. Kobetičová K, Böhm M, Jerman M, Dušek J, Černý R. Ecotoxicity and biodegradation of sustainable environment-friendly bone-glue-based adhesives suitable for insulation materials. Polymers (Basel). 2022;14(11):2209. doi:10.3390/polym14112209.
Published
How to Cite
Issue
Section
Copyright (c) 2026 MEX-ALVAREZ RAFAEL MANUEL DE JESUS, GUILLEN MORALES MARIA MAGALI, GARMA-QUE PATRICIA MARGARITA, YANEZ-NAVA DAVID, CHAN-MARTINEZ ROGER ENRIQUE, FERRER-DZUL DYLAN MANUEL
This work is licensed under a Creative Commons Attribution 4.0 International License.