Rapid UPLC-MS/MS Determination of Amantadine and Rimantadine in Human Blood and Urine for Forensic Toxicology

ShengYu Qin; Ning Wang; Di Liang; Xian Ju; LiDong Lu; LiuJiao Wu

doi:10.30560/ijas.v8n2p125

ShengYu Qin Guangxi Jingui Forensic Science Institute, China
Ning Wang Guangxi Jingui Forensic Science Institute, China
Di Liang School of Forensic Medicine, Shanxi Medical University, China
Xian Ju School of Forensic Medicine, Shanxi Medical University, China
LiDong Lu Guangxi Jingui Forensic Science Institute, China
LiuJiao Wu Guangxi Jingui Forensic Science Institute, China

DOI: https://doi.org/10.30560/ijas.v8n2p125

Keywords: Amantadine, Rimantadine, UPLC-MS/MS, forensic toxicology, method validation

Abstract

A rapid UPLC-MS/MS method was developed and validated for quantifying amantadine (AMD) and rimantadine (RIM) in human blood and urine. Sample preparation involved acetonitrile protein precipitation with amantadine-D6 as internal standard. Separation used an ACE C₁₈-PFP column and a mobile phase of 0.1% aqueous formic acid/5 mmol/L ammonium formate-acetonitrile (85:15, v/v). ESI⁺-MRM detection was employed. Acetonitrile provided optimal extraction. The method showed excellent linearity (1.0–1000.0 ng/mL; R² > 0.99), LOD/LOQ , mean recoveries (82.16–105.43%), and precision (RSD 3.57–10.39%). This sensitive, reliable method is suitable for forensic and public health applications.

References

[1] Ragshaniya, A., Kumar, V., Tittal, R. K., & Lal, K. (2024, March). Nascent pharmacological advancement in adamantane derivatives. Archives of Pharmacy (Weinheim), 357(3), e2300595. https://doi.org/10.1002/ardp.202300595
[2] Dong, G., Peng, C., Luo, J., Wang, C., Han, L., Wu, B., Ji, G., & He, H. (2015, March 13). Adamantane-resistant influenza A viruses in the world (1902–2013): Frequency and distribution of M2 gene mutations. PLoS One, 10(3), e0119115. https://doi.org/10.1371/journal.pone.0119115
[3] Gros-Louis, P., Charest, S., & Légaré, M. E. (2021, August). Late-onset bilateral epithelial ingrowth following rapid corneal decompensation owing to amantadine. Canadian Journal of Ophthalmology, 56(4), e137–e139. https://doi.org/10.1016/j.jcjo.2021.02.019
[4] Vale, J. A., & Maclean, K. S. (1977, March 5). Amantadine-induced heart failure. Lancet, 1(8010), 548. https://doi.org/10.1016/S0140-6736(77)91411-8
[5] Schwartz, M., Patel, M., Kazzi, Z., & Morgan, B. (2008, September). Cardiotoxicity after massive amantadine overdose. Medical Toxicology, 4(3), 173–179. https://doi.org/10.1007/BF03161197
[6] Cook, P. E., Dermer, S. W., & McGurk, T. (1986, November). Fatal overdose with amantadine. Canadian Journal of Psychiatry, 31(8), 757–758. https://doi.org/10.1177/070674378603100814
[7] Xu, Y., Ren, C., Han, D., Gong, X., Zhang, X., Huang, H., Jiang, F., Cui, Y., Zheng, W., & Tian, X. (2019, September 15). Analysis of amantadine in Laminaria Japonica and seawater of Daqin Island by ultra high performance liquid chromatography with positive electrospray ionization tandem mass spectrometry. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 1126–1127, 121697. https://doi.org/10.1016/j.jchromb.2019.06.024
[8] Wang, Z., Wang, X., Wang, Y., Wu, C., & Zhou, J. (2021, February 8). Simultaneous determination of five antiviral drug residues and stability studies in honey using a two-step fraction capture coupled to liquid chromatography tandem mass spectrometry. Journal of Chromatography A, 1638, 461890. https://doi.org/10.1016/j.chroma.2021.461890
[9] Ho, C., & Wong, Y. T. (2014, July–August). Fast and high throughput screening of amantadine in chicken muscle by extractive derivatization with pentafluorobenzoyl chloride and gas chromatography/negative ion chemical ionization-tandem mass spectrometry. Journal of AOAC International, 97(4), 1220–1224. https://doi.org/10.5740/jaoacint.13-245