Development and Validation of Methods Based on High-Performance Liquid Chromatography-Tandem Mass Spectrometry for Determining N-Nitrosamines Impurities in Sartan Pharmaceutical Products for Monitoring Program

Monteiro, Mychelle Alves; Lima, Patrícia Condé de; Novotný, Thiago Santana; Santana, Daniela Silva; Lima, Maria Emanuelle Damazio; Dantas, Anna Sophia Conhasco Lanzello; Santos, Laís  Oliveira dos; Souza, Matheus  Nicolau de; Maranho, Ricardo Luiz do Nascimento; Ochs, Soraya de Mendonça

doi:10.2139/ssrn.4057039

Cited by 2 publications

(3 citation statements)

References 14 publications

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“…Losartan, , Olmesartan, telmisartan, irbesartan, , candesartan, and valsartan products [14] High performance liquid chromatographytandem mass spectroscopy…”

Section: Miscellaneousmentioning

confidence: 99%

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Nitrosamine Impurities in Pharmaceutical Dosage Form: A Review

2024

IJBPAS

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The FDA and other international agencies conducted a thorough study of nitrosamine contamination in the impacted APIs and drug products after they were found in various types of drug goods. Nitrosamine impurities are potent, broad acting carcinogens which if present above the safety levels can cause serious harm. This review discusses the background of the nitrosamine reports and its chemistry. Various official and reported analytical methods for quantification of nitrosamine impurities in different drug products and drug substances are mentioned below.

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“…Losartan, , Olmesartan, telmisartan, irbesartan, , candesartan, and valsartan products [14] High performance liquid chromatographytandem mass spectroscopy…”

Section: Miscellaneousmentioning

confidence: 99%

“…Column: X Select HSS T3 (3.5μm, 100 mm, 4.6 mm) Waters Mobile phase: Water (A) and Methanol (B) both containing 0.1% formic acid Flow rate: 0.5 ml/min -1 [14] 5.…”

Section: Miscellaneousmentioning

confidence: 99%

Nitrosamine Impurities in Pharmaceutical Dosage Form: A Review

2024

IJBPAS

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“…Carcinogenicity experiments of 4-methylnitroamino-1, 3-pydinyl butanone and N-nitroso nornicotine in animals revealed that it could induce the tumors of lung, nasal cavity and liver in F344 rats, as well as the tumors of lung, trachea and nasal cavity in Syrian gold hamsters [ 3 ]. In July 2018, the German Regulatory Agency and the European Medicines Agency discontinued sales of sartan substances in Europe, since N-nitrosodimethylamine (NDMA) was detected in sartan substances [ 4 ]. Meanwhile, the US Food and Drug Administration (FDA) began to recall the related sartan products.…”

Section: Introductionmentioning

confidence: 99%

Determination of Genotoxic Impurity N-Nitroso-N-methyl-4-aminobutyric Acid in Four Sartan Substances through Using Liquid Chromatography–Tandem Mass Spectrometry

Xie¹,

Mai

Fan

2022

Molecules

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N-nitroso-N-methyl-4-aminobutyric acid (NMBA) is the third N-nitrosamine impurity found in sartans. Herein, a sensitive and stable LC-MS/MS method with multiple reactions monitoring mode has been developed for the quantitative determination of NMBA in four sartan substances. The effective separation of NMBA and sartan substances was achieved on a C18 column under gradient elution conditions. The mass spectrometry method of the atmospheric pressure chemical ionization source and internal standard method was selected as the quantitative analysis method of NMBA. Then, this proposed LC-MS/MS analysis method was validated in terms of specificity, sensitivity, linearity, accuracy, precision and stability. Good linearity with correlation coefficient over 0.99 was obtained at the NMBA concentration of 3–45 ng/mL, and the limit of quantification was 3 ng/mL. Additionally, the recoveries of NMBA in four sartan substances ranged from 89.9% to 115.7%. The intra-day and inter-day relative standard deviation values were less than 5.0%. In conclusion, this developed determination method for NMBA through liquid chromatography–tandem mass spectrometry showed the characteristics of good sensitivity, high accuracy and precision, which will be of great help for the quantitative analysis of NMBA in sartan products.

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Development and Validation of Methods Based on High-Performance Liquid Chromatography-Tandem Mass Spectrometry for Determining N-Nitrosamines Impurities in Sartan Pharmaceutical Products for Monitoring Program

Cited by 2 publications

References 14 publications

Nitrosamine Impurities in Pharmaceutical Dosage Form: A Review

Nitrosamine Impurities in Pharmaceutical Dosage Form: A Review

Determination of Genotoxic Impurity N-Nitroso-N-methyl-4-aminobutyric Acid in Four Sartan Substances through Using Liquid Chromatography–Tandem Mass Spectrometry

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