Abstract
Objective: A simple and sensitive method development and validation for the simultaneous determination of the N-nitrosamine dimethylamine (NDMA) and N Nitrosamine diethylamine (NDEA) in Olmesartan medoxomil (OLM) API and formulations by a tandem mass spectrometer (GC-MS/MS).
 Methods: Gas chromatography with a programmed oven temperature controller, Elite Wax (30 m × 0.25 mm × 0.5 μm) column, Helium as carrier gas and hyphenated to the tandem mass spectrometer powered with triple quadrupole mass analyzer, and photomultiplier tube detector. The method was validated as per the United States Food and Drug Administration (USFDA) guidelines.
 Results: With the selected GC-MS/MS conditions, the NDMA and NDEA 0.08 μg/ml (80 ng/ml) and 0.16 μg/ml (160 ng/ml) injected and Rt. for NDMA 5.634 and NDEA 6.516 min, respectively. A linear/range lies in between 0.024 and 0.120 μg/ml and 0.048 and 0.240 μg/ml for NDMA and NDEA with r2 >0.99. The precision, accuracy, and system suitability are established as per USFDA and ICH guidelines, the sensitivity of NDMA limit of detection and limit of quantification 0.08, 0.024 and NDEA 0.16, 0.048.
 Conclusion: Other nitrosamine impurities are not involved in the determination of NDMA and NDEA in the OLM using GC-MS/MS and the method is simple, sensitive, rapid, accurate, and precise.
Highlights
N nitrosamine dimethylamine (NDMA) and N nitrosamine diethylamine (NDEA) are the carcinogenic solvents on long-term usage which were found first in valsartan
Olmesartan is organic in nature and when it is dissolved in a solvent of dimethyl sulfoxide (DMS), the sample will be evaporated, leaving the Olmesartan in the vial and the solvent carries the NDMA and NDEA escaped from the headspace when exposed to gas headspace 70–240°C program temperature [3]
The present aim of work is to estimate the amount of NDMA and NDEA in the Olmesartan Medoxomil (OLM) in the API and formulations by gas chromatography-mass spectrometry (GC-MS) method and validate the method as per the United States Food and Drug Administration (USFDA) and ICH Q2R1 guidelines [5,6]
Summary
N nitrosamine dimethylamine (NDMA) and N nitrosamine diethylamine (NDEA) are the carcinogenic solvents on long-term usage which were found first in valsartan. Further study is a needed to conduct estimation of NDMA and NDEA in other sartan group of drugs. The Olmesartan Medoxomil (OLM) is of sartan expecting a presence of NDMA and NDEA in their API and formulations. Impurity assay performed by a tandem mass spectrometer to determine the NDMA and NDEA in Olmesartan is limited to 2.400 and 0.663 μg/ml in active pharmaceuticals. The present aim of work is to estimate the amount of NDMA and NDEA in the OLM in the API and formulations by gas chromatography-mass spectrometry (GC-MS) method and validate the method as per the United States Food and Drug Administration (USFDA) and ICH Q2R1 guidelines [5,6]. There were few GC MS methods for the estimation of NDMA and NDEA individually in the formulations, no method is published for the simultaneous estimation of NDMA and NDEA in the API and marketed formulations [7-35] (Fig.1-3)
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