Development, validation, and estimation of measurement uncertainty for the quantitative determination of nitrosamines in Sartan drugs using liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry

Nagendla, Narendra Kumar; Shaik, Hussain Saheb; BalaSubrahanyam, Seetha; Godugu, Deepika; Mudiam, Mohana Krishna Reddy

doi:10.1016/j.jcoa.2022.100053

Cited by 11 publications

(4 citation statements)

References 14 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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“…The linear curve was formulated for vasicine, quercetin, and lupeol by plotting the average peak area against a regression equation, and concentration was found from the plot. The R 2 was also calibrated 44,45 .…”

Section: Linearitymentioning

confidence: 99%

Analytical Method Development, Validation, and Estimation of Lupeol, Quercetin, Vasicine in Polyherbal Formulations and Selected Plant Species by using UFLC-MS

Jatoth,

Dhanabal,

Kalakotla

et al. 2024

JNR

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Background: Kabusura kudineer (KSK) is a marketed Siddha-based polyherbal formulation, and on the authority of the Govt of India, the Ministry of Ayush recommended Kabusura kudineer in the therapy of COVID-19, and due to its immuno-booster effects. Based on the “Kabusura kudineer” (KSK) formulations, we developed a “Hydaljss08” polyherbal formulation composed of 16 dried crude materials and 03 fresh forms. Both formulations contain active phytopharmaceuticals such as vasicine, quercetin, and lupeol and these are responsible for anti-viral and immunomodulatory effects, which may be due to their synergistic and additive effects. The chemical nature of vasicine is an alkaloid, quercetin is a flavonoid, and lupeol is a pentacyclic triterpenoid. Aim: The current study aims to develop and validate the analytical process for assessing vasicine, quercetin, and lupeol in both dosage forms and in a selected plant species by UFLC-MS. Methods: The ultrafast liquid chromatography study was designed by the columns of Inertsil C8, and Inertsil C18, individually, for vasicine, quercetin, and lupeol respectively. The columns and mobile phase were used as a water C18, 20 mM phosphate buffer pH 2.5: acetonitrile in a combined UFLC method development of vasicine, quercetin, and lupeol. Results: A calibration curve and adequate linearity were recorded for vasicine, quercetin, and lupeol by injecting 20.0-60.0 μg/ml, 50.0-150.0 μg/ml, and 25.0-75.0 μg/ml of marker substances. The LOD, and LOQ of the vasicine, quercetin, and lupeol were found to be 1.19, 3.60, 3.80, 11.51, 1.79, and 5.41 μg/ml, and the Ruggedness value of vasicine, lupeol, and quercetin was found in % RSD 0.4%, 0.1%, and 0.1%. Conclusion: The developed and validated method showed good linearity with a range of correlation coefficients, new, simple, novel, accurate, specificity, precision, robustness, and ruggedness are within the limits.

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“…The physical and chemical properties of N-nitrosamines are vary greatly; most can dissolve in organic solvents such as alcohol and dichloromethane, and only some compounds can dissolve in water. Therefore, the quantification of N-nitrosamines is very difficult [ 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Determination for Nine Kinds of N-Nitrosamines Compounds in Groundwater by Ultra-High-Performance Liquid Chromatography Coupled with Triple Quadrupole Mass Spectrometry

Chen

Zhang

Zhao

et al. 2022

IJERPH

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The ability to effectively detect N-nitrosamine compounds by liquid chromatography–tandem mass spectrometry presents a challenge due to the problems of high detection limits and difficulty in simultaneous N-nitrosamine compound detection. In order to overcome these limitations, this study reduced the detection limit of N-nitrosamine compounds by applying n-hexane pre-treatment to remove non-polar impurities before the conventional process of column extraction. In addition, ammonium acetate was used as the mobile phase to enhance the retention of nitrosamine target substances on the chromatographic column, with formic acid added to the mobile phase to improve the ionization level of N-nitrosodiphenylamine, to achieve the simultaneous detection of multiple N-nitrosamine compounds. Applying these modifications to the established detection method allowed the rapid and accurate detection of N-nitrosamine in water within 12 min. The linear relationship, detection limit, quantification limit and sample spiked recovery rate of nine types of nitrosamine compound were investigated, showing that the correlation coefficient ranged from 0.9985–0.9999, while the detection limits of the instrument and the method were 0.280–0.928 µg·L−1 and 1.12–3.71 ng·L−1, respectively. The spiked sample recovery rate ranged from 64.2–83.0%, with a standard deviation of 2.07–8.52%, meeting the requirements for trace analysis. The method was applied to the detection of N-nitrosamine compounds in nine groundwater samples in Wuhan, China, and showed that the concentrations of N-nitrosodimethylamine and NDEA were relatively high, highlighting the need to monitor water bodies with very low levels of pollutants and identify those requiring treatment.

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Development, validation, and estimation of measurement uncertainty for the quantitative determination of nitrosamines in Sartan drugs using liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry

Cited by 11 publications

References 14 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?

Analytical Method Development, Validation, and Estimation of Lupeol, Quercetin, Vasicine in Polyherbal Formulations and Selected Plant Species by using UFLC-MS

Simultaneous Determination for Nine Kinds of N-Nitrosamines Compounds in Groundwater by Ultra-High-Performance Liquid Chromatography Coupled with Triple Quadrupole Mass Spectrometry

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