Structural Analysis of Impurities in Aciclovir Tablets by HPLC-MS/MS

OBJECTIVE  To analysis the structures of the impurities in aciclovir tablets and the compulsory degradation samples by high performance liquid chromatography coupled with hybrid quadrupole orbitrap mass spectrometry technology (HPLC-Q-Exactive Orbitrap-MS).

METHODS  The HPLC separation was carried out on a Waters Xbridge BEH Shield RP₁₈ (4.6 mm×250 mm, 5 μm) by the gradient elution with a mobile phase consisting of 10 mmol·L^–1 ammonium formate solution (0.15% formic acid)(A) and 10 mmol·L^–1 ammonium formate solution(0.15% formic acid)-acetonitrile(50∶50)(B), and the detection wavelength was 254 nm. The Q-Exactive Orbitrap-MS was used to determine the precise first-order molecular weight and second-order fragment ions of these impurities, and the structures were identified.

RESULTS  Aciclovir and its impurities were well separated, and 8 major impurities with content>0.1% were detected and identified in aciclovir tablets and the compulsory degradation samples. Among them, 4 were the impurities listed in the European Pharmacopeia 10.0, and the others were unknown impurities identified for the first time.

CONCLUSION  The LC-MS/MS method can effectively identify the impurities in aciclovir tablets, which is significant for the production process optimization and quality control.