Development and validation of a LC-HESI MS/MS method to detect and quantify N-nitrosamines in Valsartan.
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Abstract
In the present study, a robust, efficient and sensitive LC-HESI-MS/MS method was developed and validated to simultaneously detect and quantify 5 N-nitrosamines (N-nitrosodiethylamine, N-nitrosoethylisopropylamine, N-nitrosodiisopropylamine, N-nitrosodibutylamine and N-nitrosomethylaminobutyric acid) in Valsartan, an active ingredient of the Sartan family. Chromatographic separation was achieved with an Accuore C18 column (2.6 µm, 150 x 3 mm) with gradient elution using 0.1% formic acid in water (mobile phase A) and methanol (mobile phase B). The limits of detection and quantification of N-nitrosamines ranged from 0.0337 to 0.0628 ng/mL and 0.1022 to 0.2370 ng/mL, respectively, demonstrating the high sensitivity and quantitative capability of the method. The recovery of N-nitrosamines ranged from 70% to 130%, and the repeatability and intermediate precision had coefficients of variation less than 10%, evaluated on the Pertena Complete product containing 3 active pharmaceutical ingredients (Amlodipine, Hydrochlorothiazide and Valsartan). Calibration curves were constructed in a range of 1.0 to 15.0 ng/mL, obtaining coefficients of determination (R2) greater than 0.995. Statistics played a crucial role in this study, allowing the determination of the precision, accuracy and reliability of the method through analysis of variance, linearity studies and the construction of confidence intervals. This study confirms the safety of the Pertena Complete product, manufactured by Prophar SA, and highlights the effectiveness of the method for an accurate and reliable analysis of the active pharmaceutical ingredient.
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Carlos Andrés Reina-Velasco , Universidad Politécnica Estatal del Carchi - Ecuador
https://orcid.org/0009-0006-2632-4822
I´m a chemist by profession and I am finishing my master's degree in applied statistics at UPEC. Currently, I work in a pharmaceutical company where I have held the positions of validation analyst and, currently, research and development analyst. In these areas, my interest in statistics was born, which led me to pursue a master's degree in this field. My goal is to demonstrate that statistics is a fundamental science that complements all careers and to highlight its importance in various fields, especially in chemistry.
Carlos Alberto Brito-Dumancela , Universidad Central del Ecuador - Ecuador
https://orcid.org/0000-0002-7371-5141
Master in Applied Statistics and Chemistry from the Central University of Ecuador, I have a diploma in Scientific Research from UNIANDES University, with experience in the areas of experimental design, data analysis, applied mathematics, statistical modeling and research methodology. My work experience was developed in the public and private sector, in areas related to research and product development, process improvement, advice on the proper application of statistical methods in undergraduate and graduate theses in science and engineering careers.
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