Cost Effective Accurate and Precise Analytical Method Development of Content Estimation of N-Nitrosodimethyl Amine and N-Nitrosodiethyl Amine in Olmesartan Medoxomil by GC-MS
A simple, precise and accurate GCMS method was developed for estimation the content estimation of N-Nitrosodimethylamine (NDMA) & N-Nitrosodiethylamine (NDEA) in olmesartan medoxomil (OLM) in drug substances. The content was determined by GCMS on DB-CAM 30.0 m Χ 0.32 mm, 0.5µm Capillary column and helium was used as carrier gas, using methanol as diluent at column flow rate of 2.0 mL/min and Ion source temperature & Interface temperature at 200ºC and Detector gain mode relative to tuning file with acquisition mode Q3 SIM. The method was developed and evaluated for validation parameter as per ICH guidelines for Specificity, linearity, accuracy and precision. The method shows good linearity over the range of 10%-150% for NDMA and NDEA for olmesartan. The average percentage recoveries were found within predefined acceptance criteria (10% and 100%) for N-Nitrosodimethylamine (NDMA) & N-Nitrosodiethylamine (NDEA) in olmesartan medoxomil, respectively. Therefore, the proposed method can be applied for routine analysis of the bulk drugs as well as combined pharmaceutical dosage forms of olmesartan medoxomil.
Keywords: Olmesartan medoxomil (OLM), N-Nitrosodimethylamine (NDMA) &, N-Nitrosodiethylamine (NDEA) GCMS, Validation, Analytical validation.
2. British pharmacopoeia: The Stationery Office, London. 2007; 1036-103
3. Huber, L. Validation of analytical methods, in: Validation and Qualification in the Analytical Laboratories, Interpharm Press, Buffalo Grove, IL, 1998; 11:107-115.
4. ICH. Text on Validation of Analytical Procedures, in: International Conference on Harmonization of Technical Requirements for Registration of Pharmaceutical for Human Use, Geneva 2000.
5. ICH. Validation of Analytical Procedure: Methodology, in: International Conference on Harmonization of Technical Requirements for Registration of Pharmaceutical for Human Use, Geneva 2005.
6. Nitrosamines impurities in human medicinal products and related guidance. European medicine Agency. CHMP/428592/2019. 2020.
7. French National Agency for Medicines and Health Products Safety Laboratory Controls Division – French OMCL Method reference: 19A0416-01, Determination of NDMA and NDEA in SARTAN drug substances by HPLC/UV,www.ansm.sante.fr. April, 2020.
8. Schmidtsdorff, S., Schmidt, A.H. Simultaneous detection of nitrosamines and other sartan-related impurities in active pharmaceutical ingredients by supercritical fluid chromatography, J. Pharm. Biomed. Anal. 2019; 174:151–160.
9. The General European OMCL Network, LC-MS/MS Method for the determination of NDEA and NDMA in Valsartan, Irbesartan and Losartan APIs and finished dosage form 2020.
10. Sorgel, F, Kinzig M, Abdel-Tawab, M, Bidmon, C, Schreiber, A, Ermel, S, Wohlfart, j, Besa, A, Scherf-Clavel, O, Holzgrabe, U. The contamination of valsartanof valsartan and other sartans, part 1: new findings, J. Pharm. Biomed. Anal. 2019; 192:395–405.
11. US FDA. Combined Direct Injection N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) Impurity Assay by GC/MS 2018.
12. Combined direct injection method: a GC-MS/MS method that allows for determination of both NDMA and NDEA simultaneously (https://www.fda.gov/media/123409/download) OTR has been asked to develop a gas chromatography-tandem mass spectrometry (GC-MS/MS) method utilizing liquid injection to look for all these nitrosamine impurities. www.fda.gov/media/123409.April, 2020.
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