Development and Validation of a Method for the Semi-Quantitative Determination of N-Nitrosamines in Active Pharmaceutical Ingredient Enalapril Maleate by Means of Derivatisation and Detection by HPLC with Fluorimetric Detector

A novel HPLC method with fluorimetric detection was developed for the determination of potentially carcinogenic N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) in active pharmaceutical ingredient enalapril maleate. N-nitrosamines were subject to denitrosation followed by derivatisation dansyl chloride or fluorenylmethoxycarbonyl (Fmoc-Cl). Fmoc-Cl offers much better sensitivity repeatability than derivatisation. satisfactory linearity obtained method, R2 = 0.9994 NDMA 0.9990 NDEA, a limit quantification level 0.038 μg/g 0.050 NDEA. The precision decreased concentration maximum about 10%. recoveries range 74.2 ± 4.2% 101.6 16.1% 90.6 2.9% 125.4 7.4% Dansyl found be an inappropriate agent, mainly due potential contamination dimethylamine, leading unrepeatable peaks blank solution. Since involves amines liberated from N-nitrosamines, it necessary remove test sample. Several critical points standard/sample preparation have been mentioned, which affect reproducibility are not covered similar articles.