Dr. Mohana Vamsi Nuli is an accomplished pharmaceutical professional and researcher with over 18 years of experience in pharmaceutical analysis, quality assurance, analytical method development, validation, and pharmaceutical manufacturing. He currently works at Penn Life Sciences, Pennsylvania, USA, and has previously held positions at leading organizations, including Sanofi, Dr. Reddy’s Laboratories, Wockhardt, Hospira, and Aurobindo Pharma.

He holds a Ph.D. in Pharmaceutical Sciences from Rayalaseema University, an M.Pharm in Quality Assurance and Analysis, and a B.Pharm degree. His expertise includes analytical quality by design (AQbD), HPLC and LC–MS/MS method development, regulatory compliance, stability studies, and pharmaceutical product quality management.

Dr. Nuli has authored numerous scientific publications in reputed journals and contributed to several textbooks and book chapters published by internationally recognized publishers, including Springer Nature and Elsevier. He has received multiple research awards, serves on editorial boards of scientific journals, and has reviewed more than 120 research articles. His research focuses on pharmaceutical analytical sciences, sustainable analytical methodologies, drug development, and quality assurance.

Eco-Friendly Quality by Design-Based LC–MS/MS Method for the Determination of Nitrosamine Impurities in Triamcinolone Acetonide Pharmaceutical Products

Abstract: Purpose Nitrosamine impurities are highly potent genotoxic contaminants that present significant safety concerns in phar maceutical products,necessitating sensitive, robust, and environmentally sustainable analytical methods for their trace-level determination. This study aimed to develop, optimize, and validate an Analytical Quality by Design (AQbD)-based liquid  chromatography–tandem mass spectrometry (LC–MS/MS) method for the simultaneous quantification of seven nitrosa mine impurities—N-nitrosodimethylamine (NDMA), Nnitrosodiethylamine (NDEA), N-nitrosodibutylamine (NDBA), N-nitroso-Nmethylpropylamine (NMPA), N-nitrosomethyl-4-aminobutyric acid (NMBA), Nnitrosodiisopropylamine (NDIPA), and N-nitrosoethylisopropylamine (NEIPA)—in triamcinolone acetonide (TAA) drug substance and pharmaceuti cal formulations. Methods The analytical method was systematically developed using the AQbD framework by identifying and optimizing critical analytical parameters to achieve robust chromatographic performance. Chromatographic separation was performed on a Waters ACQUITY™ BEH C18 (50 × 2.1 mm, 1.7 μm) column using gradient elution with acetonitrile and 0.1% (v/v) formic acid in water at a flow rate of 0.8 mL min⁻¹. Detection was carried out in positive electrospray ionization mode  using multiple reaction monitoring (MRM). The method was validated according to regulatory guidelines for linearity, accuracy, precision, and sensitivity. Environmental sustainability was  evaluated using ComplexGAPI, AGREE, AGREEprep, Analyti cal Eco-Scale, and White Analytical Chemistry metrics. Results The optimized LC–MS/MS method achieved complete chromatographic separation of all seven nitrosamine impuri ties within 10 min. The method exhibited excellent linearity over the concentration range of 100–500 ng mL⁻¹ (r² > 0.999),high precision (%RSD < 2%), and satisfactory accuracy with recoveries ranging from 98.2% to 101.4%. Greenness assess ment demonstrated excellent environmental sustainability and overall analytical performance. Application of the method to commercially available triamcinolone acetonide drug substance and formulations revealed no detectable levels of the investigated nitrosamine impurities. Conclusion The proposed AQbD-driven LC–MS/MS method is rapid, robust, highly sensitive, and environmentally sustain able for the simultaneous determination of seven nitrosamine impurities in triamcinolone acetonide. Its excellent analytical performance and green credentials make it a suitable platform for routine pharmaceutical quality control, regulatory compli ance, and impurity surveillance. 

Keywords: Nitrosamine impurities · LC–MS/MS · Triamcinolone acetonide · Quality by Design · Green analytical chemistry · Analytical whiteness