Objective: To identify the related substances in aciclovir tablets by LC-Q-TOF/MS. Methods: The separation of the related substances in aciclovir tablets were carried out on an ODS (250 mm×4.6 mm,5 μm) column with gradient elution using 0.15% formic acid 10 mmol·L-1 ammonium formate buffer solution and acetonitrile as mobile phases. The accurate mass and elemental composition of the parent ions and their product ions of the related substances were determined by electrospray-ionization quadrupole time-of-flight high resolution mass spectrometry. The structures of the related substances were elucidated. Results: Under the established LC-Q-TOF/MS condition, aciclovir and its related substances were adequately separated, and 23 major related substances including 7 known impurities specified in the EP were detected and identified in aciclovir tablets and its stressed samples. Conclusion: The results can provide reference for the quality control of aciclovir tablets.
WANG Li-jie, LIN Dong-xiang, ZHU Mi-qun, LU Yu-ting, SONG Min, HANG Tai-jun
. Identification of the related substances in aciclovir tablets by LC-Q-TOF/MS*[J]. Chinese Journal of Pharmaceutical Analysis, 2023
, 43(8)
: 1381
-1393
.
DOI: 10.16155/j.0254-1793.2023.08.14
[1] ELION GB, FURMAN PA, FYFE JA, et al. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl)guanine [J].Proc Natl Acad Sci USA, 1977, 74(12):5716
[2] SCHALKWIJK HH, SNOECK R, ANDREI G. Acyclovir resistance in herpes simplex viruses: prevalence and therapeutic alternatives [J].Biochem Pharmacol, 2022, 206:115322
[3] KATARZYNA K, ANETA P, ANNA K, et al. Acyclovir in the treatment of herpes viruses-a review [J].Curr Med Chem, 2020, 27(24):4118
[4] WEI YP, YAO LY, WU YY, et al. Critical review of synthesis, toxicology and detection of acyclovir [J].Molecules, 2021, 26(21):6566
[5] 中华人民共和国药典2020年版.二部[ S ]. 2020: 679
ChP 2020.VolⅡ [S]. 2020: 679
[6] USP 43-NF 38: Vol 45 [S]. 2020: 88
[7] EP 10.0. VolⅡ [S]. 2020: 1758
[8] JIA TC, GUO JT, WANG Z, et al. Photodegradation mechanisms of acyclovir in water and the toxicity of photoproducts [J].J Rad Nucl Chem, 2019, 320(3):823
[9] 王文晞, 谢育媛, 徐小玲, et al. 阿昔洛韦口服固体制剂质量分析 [J].中国药师, 2020, 23(10):2071
WANG WX, XIE YY, XU XL, et al. Quality analysis of aciclovir oral solid preparation[J].China Pharm, 2020, 23(10):2071
[10] AN T, AN J, GAO Y, et al. Photocatalytic degradation and mineralization mechanism and toxicity assessment of antivirus drug acyclovir: experimental and theoretical studies [J].Appl Catal B Environ, 2015, 164:279
[11] SUÁREZ RM, MATÍA MP, NOVELLA JL, et al. Synthesis of 9,9′-[1,2-ethanediylbis(oxymethylene)]bis-2-amino-1, 9-dihydro-6H-purin-6-one, an impurity of acyclovir [J].Molecules, 2012, 17(8):8735
[12] HUIDOBRO AL, RUPEREZ FJ, BARBAS C. LC methods for acyclovir and related impurities determination [J].J Pharm Biomed Anal, 2005, 37(4):687
[13] BINDRA DS, WILLIAMS TD,STELLA VJ. Degradation of O6-benzylguanine in aqueous polyethylene glycol 400 (PEG 400) solutions: concerns with formaldehyde in PEG 400 [J].Pharm Res, 1994, 11(7):687
[14] BEJGUM BC, JOHNSON PR, STAGNER WC. Acyclovir chemical kinetics with the discovery and identification of newly reported degradants and degradation pathways involving formaldehyde as a degradant and reactant intermediate [J].Int J Pharm, 2018, 535(1-2):172
[15] 熊东路, 莫志文, 杨轩, et al. 一种制备双(二甲氧基乙氧基)甲烷的方法:中国, CN110511124A [P]. 2019-11-29
XIONG DL, MO ZW, YANG X, et al. Preparation Method of Bis (dimethoxyethoxy) Methane: China,CN110511124A [P]. 2019-11-29