Development and validation of rapid ultra high performance liquid chromatography with tandem mass spectroscopic method for the quantification of N‐nitrosodimethyl amine and N‐nitrosodiethyl amine in sitagliptin and metformin hydrochloride immediate and extended‐release formulations

Mallavarapu, Ravindra; Katari, Naresh Kumar; Siddhani, Vijaya Krishna; Marisetti, Vishnu Murthy; Rekulapally, Vijay Kumar; Vyas, Govind; Jonnalagadda, Sreekantha B.

doi:10.1002/jssc.202200226

Cited by 12 publications

(7 citation statements)

References 12 publications

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“…The current N -nitrosamine risk assessment approach − in the pharmaceutical industry consists of paper-based evaluation of synthetic routes and subsequent GC-MS and/or LC-MS analysis − of drug substances and drug products considered to be under risk for N -nitrosamine contamination. The current instrumental analytical methods that can quantify N -nitrosamines in levels below ppm region are time-consuming and expensive, require highly skilled personnel, and require development of the specific analytical method for each individual N -nitrosamine and each drug product.…”

Section: Introductionmentioning

confidence: 99%

Does the Red Shift in UV–Vis Spectra Really Provide a Sensing Option for Detection of N-Nitrosamines Using Metalloporphyrins?

Trampuž¹,

Žnidarič²,

Gallou

et al. 2022

ACS Omega

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N-nitrosamines are widespread cancerogenic compounds in human environment, including water, tobacco products, food, and medicinal products. Their presence in pharmaceuticals has recently led to several recalls of important medicines from the market, and strict controls and tight limits of N-nitrosamines are now required. Analytical determination of N-nitrosamines is expensive, laborious, and time-inefficient making development of simpler and faster techniques for their detection crucial. Several reports published in the previous decade have demonstrated that cobalt porphyrin-based chemosensors selectively bind N-nitrosamines, which produces a red shift of characteristic Soret band in UV–Vis spectra. In this study, a thorough re-evaluation of metalloporphyrin/N-nitrosamine adducts was performed using various characterization methods. Herein, we demonstrate that while N-nitrosamines can interact directly with cobalt-based porphyrin complexes, the red shift in UV–Vis spectra is not selectively assured and might also result from the interaction between impurities in N-nitrosamines and porphyrin skeleton or interaction of other functional groups within the N-nitrosamine structure and the metal ion within the porphyrin. We show that pyridine nitrogen is the interacting atom in tobacco-specific N-nitrosamines (TSNAs), as pyridine itself is an active ligand and not the N-nitrosamine moiety. When using Co(II) porphyrins as chemosensors, acidic and basic impurities in dialkyl N-nitrosamines (e.g., formic acid, dimethylamine) are also UV–Vis spectra red shift-producing species. Treatment of these N-nitrosamines with K2CO3 prevents the observed UV–Vis phenomena. These results imply that cobalt-based metalloporphyrins cannot be considered as selective chemosensors for UV–Vis detection of N-nitrosamine moiety-containing species. Therefore, special caution in interpretation of UV–Vis red shift for chemical sensors is suggested.

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Section: Introductionmentioning

confidence: 99%

Does the Red Shift in UV–Vis Spectra Really Provide a Sensing Option for Detection of N-Nitrosamines Using Metalloporphyrins?

Trampuž¹,

Žnidarič²,

Gallou

et al. 2022

ACS Omega

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“…particularly in pharmacy [2][3][4][5][6][7], for example, in the recent analysis of traditional Chinese medicine [8][9][10][11][12][13][14][15][16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

“…This allows even higher theoretical plate numbers and even faster separations. Therefore, UHPLC is a popular technique where highly complex separations are required, particularly in pharmacy [2–7], for example, in the recent analysis of traditional Chinese medicine [8–21].…”

Section: Introductionmentioning

confidence: 99%

Performance in (Ultra‐)high‐performance liquid chromatography—How to qualify and optimize instruments in practice

Jaekel

Wirtz

Lamotte

et al. 2023

J of Separation Science

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This paper investigates the suitability of an ultra‐high‐performance liquid chromatography/high‐performance liquid chromatography hybrid system for ultra‐high‐performance liquid chromatography applications. Thus, the effect of extra column band broadening, the gradient system, and the injection system were tested and optimized according to their capabilities. An increase of the theoretical plate number up to a factor of two is achieved by the optimization of the extra column volume into the typical ultra‐high‐performance liquid chromatography range (<10 μl). Moreover, for qualitative purposes injections of volumes typical for ultra‐high‐performance liquid chromatography methods are precise. Despite this, a lack of precision and accuracy was determined for the gradient system, and the dwell volume meets the typical specification range for conventional HPLC systems. Therefore, hybrid systems are the intercept between both spectra and are limitedly suitable for ultra‐high‐performance liquid chromatography applications. Another way to approximate ultra‐high‐performance liquid chromatography performance using a high‐performance liquid chromatography system is superficially porous particles. Thus, H/u curves of 5 μm superficially porous and 3 μm fully porous particles were recorded in order to determine the effect of the particle technology resulting in comparable performance of the used stationary phases.

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“…N-nitrosamines are typically determined by GC-MS or LC-MS using the simple diluting and shooting approach [15][16][17][18][19][20]. Although fast and straightforward, that methodology entails the injection of dirty extracts into the chromatographic system and can lead to column clogging, instrument contamination, and carry-over effects.…”

Section: Introductionmentioning

confidence: 99%

Microextraction by packed sorbent of N‐nitrosamines from Losartan tablets using a high‐throughput robot platform followed by liquid chromatography‐tandem mass spectrometry

Santos

Medina

Lanças

2023

J of Separation Science

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The development of a fast, cost-effective, and efficient microextraction by packed sorbent setup was achieved by combining affordable laboratory-repackable devices of microextraction with a high-throughput cartesian robot. This setup was evaluated for the development of an analytical method to determine Nnitrosamines in losartan tablets. N-nitrosamines pose a significant concern in the pharmaceutical market due to their carcinogenic risk, necessitating their control and quantification in pharmaceutical products. The parameters influencing the performance of this sample preparation for N-nitrosamines were investigated through both univariate and multivariate experiments. Microextractions were performed using just 5.0 mg of carboxylic acid-modified polystyrene divinylbenzene copolymer as the extraction phase. Under the optimized conditions, the automated setup enabled the simultaneous treatment of six samples in less than 20 min, providing reliable analytical confidence for the proposed application. The analytical performance of the automated high-throughput microextraction by the packed sorbent method was evaluated using a matrix-matching calibration. Quantification was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry with chemical ionization at atmospheric pressure. The method exhibited limits of detection as low as 50 ng/g, good linearity, and satisfactory intra-day (1.38-18.76) and inter-day (2.66-20.08) precision. Additionally, the method showed accuracy ranging from 80% to 136% for these impurities in pharmaceutical formulations.

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Development and validation of rapid ultra high performance liquid chromatography with tandem mass spectroscopic method for the quantification of N‐nitrosodimethyl amine and N‐nitrosodiethyl amine in sitagliptin and metformin hydrochloride immediate and extended‐release formulations

Cited by 12 publications

References 12 publications

Does the Red Shift in UV–Vis Spectra Really Provide a Sensing Option for Detection of N-Nitrosamines Using Metalloporphyrins?

Does the Red Shift in UV–Vis Spectra Really Provide a Sensing Option for Detection of N-Nitrosamines Using Metalloporphyrins?

Performance in (Ultra‐)high‐performance liquid chromatography—How to qualify and optimize instruments in practice

Microextraction by packed sorbent of N‐nitrosamines from Losartan tablets using a high‐throughput robot platform followed by liquid chromatography‐tandem mass spectrometry

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