Current status and prospects of development of analytical methods for determining nitrosamine and N-nitroso impurities in pharmaceuticals

Wichitnithad, Wisut; Nantaphol, Siriwan; Noppakhunsomboon, Kachathong; Thitikornpong, Worathat; Rojsitthisak, Pornchai

doi:10.1016/j.talanta.2022.124102

Cited by 17 publications

(5 citation statements)

References 52 publications

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“… 98 These nitrosyl compounds have potential carcinogenic, teratogenic, and mutagenic effects on the human body. 99 The European Food Safety Authority (EFSA) has set the Acceptable Daily Intake (ADI) for nitrates and nitrites at 3.7 mg and 0.07 mg per kilogram of body weight, respectively. 100 , 101 Similar to other clinical pharmacotherapies, nitrates have a specific dose-response range that defines their pharmacological activity.…”

Section: Methodsmentioning

confidence: 99%

Dietary Beetroot Juice – Effects in Patients with COPD: A Review

Chen,

Chang,

et al. 2024

COPD

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Chronic Obstructive Pulmonary Disease (COPD) exerts a severe toll on human health and the economy, with high prevalence and mortality rates. The search for bioactive components effective in the treatment of COPD has become a focal point of research. Beetroot juice, readily accessible and cost-effective, is noted for its ability to enhance athletic performance and for its preventive and therapeutic impact on hypertension. Beetroot juice is a rich source of dietary nitrates and modulates physiological processes via the nitrate-nitrite- nitric oxide pathway, exerting multiple beneficial effects such as antihypertensive, bronchodilatory, anti-inflammatory, antioxidant, hypoglycemic, and lipid-lowering actions. This paper provides a review of the existing research on the effects of beetroot juice on COPD, summarizing its potential in enhancing exercise capacity, lowering blood pressure, improving vascular function, and ameliorating sleep quality among patients with COPD. The review serves as a reference for the prospective use of beetroot juice in the symptomatic improvement of COPD, as well as in the prevention of exacerbations and associated comorbidities.

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Section: Methodsmentioning

confidence: 99%

Dietary Beetroot Juice – Effects in Patients with COPD: A Review

Chen,

Chang,

et al. 2024

COPD

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“…Despite the aforementioned benefits of CDDS, concerns have been raised about the quality of some CR generic medications [13,14]. This has led to several recalls, including Pharmaceuticals 2024, 17, 271 2 of 15 orphenadrine citrate CR tablets [13], propoxyphene CR capsules [14], fentanyl HCL CR tablets [15], and dronabinol CR capsules [16]. The reasons behind these recalls remain ambiguous for some medications.…”

Section: Introductionmentioning

confidence: 99%

Effect of Hydration Forms and Polymer Grades on Theophylline Controlled-Release Tablet: An Assessment and Evaluation

Sakkal,

Arafat,

Yuvaraju

et al. 2024

Pharmaceuticals

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Background: Drug release from controlled release delivery systems is influenced by various factors, including the polymer’s grade and the drug’s hydration form. This study aimed to investigate the impact of these factors on the controlled release of theophylline (THN). This research compares the monohydrate form found in branded products with the anhydrous form in generic equivalents, each formulated with different polymer grades. Methods: Quality control assessment was conducted alongside in vitro evaluation, complemented by various analytical techniques such as X-ray diffraction (XRD) and scanning electron microscopy (SEM). Additionally, thermal analyses using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were employed. Results: Quality control assessments demonstrated that the generic tablets exhibited lower average weight and resistance force compared to the branded ones. In vitro tests revealed that generic tablets released contents within 120 min, compared to 720 min for the branded counterpart. Characterization using XRD and SEM identified disparities in crystallinity and particle distribution between the three samples. Additionally, the thermal analysis indicated consistent endothermic peaks across all samples, albeit with minor variations in heat flow and decomposition temperatures between the two products. Conclusions: This study demonstrated that variations in polymer grade and hydration form significantly impact THN release.

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“…In recent years, the presence of a carcinogenic impurity in pharmaceuticals, exemplified by N-nitrosodimethylamine, has raised significant public concerns [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Carcinogenic impurities can potentially form during the production and storage of active pharmaceutical ingredients (APIs) and drug products [18].…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of a Solvent-Free Headspace GC-MS Method for the Screening of Benzyl Chloride in Pharmaceutical Products

Song,

Min,

Kim

et al. 2023

Chemosensors

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This study presents a solvent-free headspace gas chromatography–mass spectrometry (SF-HS-GC/MS) method for robustly screening benzyl chloride, a mutagenic carcinogen, impurities in active pharmaceutical ingredients (APIs) and drug products. The SF-HS-GC/MS method simplifies analysis by eliminating solvent use, reducing matrix interference. Optimized headspace parameters include incubation temperature, time, and sample amount. Validation, aligned with Q2(R1) ICH guidelines and ICH M7 recommendations, covers selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, system suitability, and robustness. Employing a DB-5MS column (30 m × 0.25 mm, 0.25 µm) with solvent-free split injection, the method’s calibration curve (0.05–5 μg/g) exhibits a strong correlation (>0.9998). The LOQ was 0.1 μg/g, with precision (%CV) consistently <5% and accuracy within 95–105%. Furthermore, an investigation confirmed the absence of artefactual benzyl chloride formation in drug products under headspace conditions. The developed SF-HS-GC/MS method successfully screened benzyl chloride in cinnarizine drug substances and products.

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Current status and prospects of development of analytical methods for determining nitrosamine and N-nitroso impurities in pharmaceuticals

Cited by 17 publications

References 52 publications

Dietary Beetroot Juice – Effects in Patients with COPD: A Review

Dietary Beetroot Juice – Effects in Patients with COPD: A Review

Effect of Hydration Forms and Polymer Grades on Theophylline Controlled-Release Tablet: An Assessment and Evaluation

Development and Validation of a Solvent-Free Headspace GC-MS Method for the Screening of Benzyl Chloride in Pharmaceutical Products

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