Affiliation:
1. College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China
2. Chongqing Pharmaceutical Preparation
Engineering Technology Research Center, Chongqing Medical and Pharmaceutical College, Chongqing,
401331, China
Abstract
Background:
N-nitrosodimethylamine (NDMA) are a sort of genotoxic impurities
(GTIs) having strong carcinogenic effects and obvious hepatotoxicity. To monitor the NDMA
content of metformin hydrochloride sustained-release tablets and enteric capsules in China
from 2018 to 2022, a GC-MS/MS method was established and validated.
Materials and Methods:
The chromatographic column was Agilent VF-WAXms capillary column
(30 m×0.25 mm, 0.25 μm). The GC-MS/MS method was equipped with multiple reaction
monitoring (MRM) modes. To assess the quantity of NDMA, the molecular ion at mass-tocharge
(m/z) of 74-44 was monitored under the 6 V collision energy, and to assess the quality
of NDMA monitoring, the molecular ions at m/z 74-42 were determined. A total of 143 batches
of metformin hydrochloride-finished products from 35 enterprises were determined by
this method
Results:
The linear range of the method was 0.25 ~ 50.00 ng/mL, r = 0.9998, S/N > 10, and the
limit of detection and quantitation were 0.06 ng/mL and 0.21 ng/mL, respectively. The average
recovery was 98.62%, and the RSD was 4.31%. All batches of enteric capsules met the requirements;
38.21% of the 123 batches sustained-release tablets still exceeded the acceptable daily
intake.
Conclusion:
The presented method is sensitive, accurate, precise, and available for both enteric
capsules and sustained-release tablets of metformin hydrochloride, which can provide a reference
for their quality control. The over-limit phenomenon of NDMA in metformin hydrochloride
products poses new challenges and requirements for both the State Drug Administration
and enterprises.
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmaceutical Science,Molecular Medicine,Biochemistry,Biophysics