Nitrosamine Impurities Method Development & Validation
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- Nitrosamine Impurities Method Development & Validation
Focus on Impurity Profiling Elemental to Organic
Facility : Received EIR report from USFDA. Maharashtra FDA Approved
Instruments : LC-MS/MS with PDA Detector with chromeleon Software ICP-MS.
Analytical Services
Genotoxic Impurities as per ICH M7 Method Development, Method Validation & Sample Analysis Mass Identification By Direct Infusion & BY LCMSMS
Elemental Analysis Elemental Impurities as per USP<232>/<233> & ICH Q3D guidelines
Extractables & Leachables
Nitrosamine Impurities Method Development & Validation
ESTIMATION OF NITROSAMINE IMPURITIES (NDMA, NDEA, NMBA, NIEPA, NDIPA, NDBA and NMPA) By LC-MS/MS
Nitrosamine Impurities in Metformin ER Tablet: Nitrosamines are organic compounds of the chemical structure R2N–N=O, where R is usually an alkyl group. The feature a nitroso group (NO+) bonded to an deprotonated amine. Most nitrosamines are carcinogenic.
They are usually produced by the reaction of nitrous acid (HNO2) and secondary amines.
HONO + R2NH → R2N-NO + H2O
Nitrosamines are produced by the reaction of nitrites and secondary amines. Nitrites are used as food preservatives, e.g. cured meats. Secondary amines arise by the degradation of proteins (food).
Nitrite and nitrosamine intake are associated with risk of gastric cancer and o esophageal cancer.
Some Nitrosamines are as follows:
NDMA i.e. N-nitrosodimethylamine
NDEA i.e. N-nitrosodiethylamine
NEIPA i.e. N-nitrosoethylIsopropylamine
NDIPA i.e. N-nitrosodiIsopropylamine
NMPA i.e. N-nitrosomethylphenylamine
NDBA i.e. N-nitrosodibutylamine
NMBA i.e. N-nitrosomethyl butyric acid
These impurities can come from FOOD, Water and Soil as well.
Nalanda Research Laboratories developed the analytical method to estimate the Nitrosamine impurities by LCMS/ MS and achieved the LOD & LOQ as follows:
Guidance to avoid nitrosamines in human medicines
In September 2019 EMA began a review under Article 5(3) of Regulation (EC) No 726/2004 to provide guidance to marketing authorisation holders on how to avoid the presence of nitrosamine impurities in human medicines. As part of this review, the CHMP has requested marketing authorisation holders for human medicines containing chemically synthesised active substances to review their medicines for the possible presence of nitrosamines and test all products at risk.
Nitrosamines EMEA-H-A5(3)-1490 – Information on nitrosamines for marketing authorisation holders (PDF/100.46 KB)
Nalanda Research Laboratories Achieved LOQ 0.01ppm and Actual concentration achieved is 0.001ppm for Nitrosamine Impurities
Interim Limits for NDMA, NDEA, and NMBA in Angiotensin II Receptor Blockers. (ARBs)
- 1 . The acceptable intake is a daily exposure to a compound such as NDMA, NDEA, or NMBA that approximates a 1:100,000 cancer risk after 70 years exposure.
- 2 . These values are based on a drug’s maximum daily dose as reflected in the drug label.
- 3 . FDA is temporarily not objecting to losartan with NMBA below 9.82 ppm remaining on the market.
