N-Nitrosodimethylamine Contamination in the Metformin Finished Products

A GC–MS/MS method with EI ionization was developed and validated to detect and quantify N-nitrosodimethylamine (NDMA) and seven other nitrosamines in 105 samples of metformin tablets from 13 different manufactures. Good linearity for each compound was demonstrated over the calibration range of 0.5–9...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Vol. 25; no. 22; p. 5304
Main Authors: Zmysłowski, Adam, Książek, Iza, Szterk, Arkadiusz
Format: Journal Article
Language:English
Published: Switzerland MDPI 13.11.2020
MDPI AG
Subjects:
Calibration
Dimethylnitrosamine - chemistry
Drug Contamination
Drug Design
Europe
Gas Chromatography-Mass Spectrometry
GC-MS
Limit of Detection
Linear Models
metformin
Metformin - analysis
Metformin - chemistry
NDMA
nitrosamines
Pharmaceutical Preparations - analysis
Powders
Solvents
Tablets
Tandem Mass Spectrometry
Temperature
Europe
GC-MS
metformin
nitrosamines
NDMA
ISSN:1420-3049, 1420-3049
Online Access:Get full text
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Summary:A GC–MS/MS method with EI ionization was developed and validated to detect and quantify N-nitrosodimethylamine (NDMA) and seven other nitrosamines in 105 samples of metformin tablets from 13 different manufactures. Good linearity for each compound was demonstrated over the calibration range of 0.5–9.5 ng/mL. The assay for all substances was accurate and precise. NDMA was not detected in the acquired active pharmaceutical ingredient (API); however, NDMA was detected in 64 (85.3%) and 22 (91.7%) of the finished product and prolonged finished product samples, respectively. European Medicines Agency recommends the maximum allowed limit of 0.032 ppm in the metformin products. Hence, 28 finished products and 7 pronged dosage products were found to exceed the acceptable limit of daily intake of NDMA contamination. The implications of our findings for the testing of pharmaceutical products are discussed.
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ISSN:1420-3049
1420-3049
DOI:10.3390/molecules25225304