Objective: To identify the structures of the related substances in penciclovir cream by two-dimensional liquid chromatography quadrupole time-of-flight tandem mass spectrometry (2D-LC-Q TOF/MS) technique. Methods: The first-dimension separation of the related substances in penciclovir cream and its stressed samples according to ICH were carried out on an ODS (250 mm×4.6 mm, 5 μm) column with gradient elution by 0.15% formic acid 10 mmol·L-1 ammonium formate buffer solution and acetonitrile as mobile phases, and each related substance was enriched separately. The second-dimension gradient elution was performed on a Phenomenex Luna SCX (250 mm×4.6 mm, 5 μm) column with 0.1% formic acid 20 mmol·L-1 ammonium formate buffer solution and acetonitrile as mobile phases for each of the related substances to achieve good separation with the matrix of penciclovir cream. The accurate mass and elemental composition of the parent ions and their product ions of the related substances were determined by positive electrospray-ionization quadrupole time-of-flight high resolution mass spectrometry, and the structures of all the related substances were elucidated. Results: Under the established 2D-LC-Q TOF/MS analytical conditions, penciclovir and its related substances were adequately separated, and 21 major related substances were detected and identified in the penciclovir cream and its stressed samples. According to their chromatographic retention behavior, spectral characteristics, mass spectrometry characteristics and their differences from other known related substances of nucleoside drugs and combing with synthesis and formulation process route, their structures can be identified all of which were identified for the first time. Conclusion: The results can provide reference for the quality control of penciclovir cream.
Abbosova Zokirjonovna Diyorakhon, WANG Li-jie, LU Yu-ting, SONG Min, HANG Tai-jun
. Identification of the related substances in penciclovir cream by two-dimensional LC-MS techniques*[J]. Chinese Journal of Pharmaceutical Analysis, 2024
, 44(1)
: 89
-100
.
DOI: 10.16155/j.0254-1793.2024.01.09
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