The probable carcinogenic nitrosamine impurities, such as N-nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA), have been detected from various pharmaceuticals in recent years. The sensitive chromatographic methods, including liquid chromatography (LC) and gas chromatography (GC), have been applied for analyzing nitrosamines in the pharmaceutical substrates, such as sartans, ranitidine and metformin. In comparison of LC, the efficacy of GC for analyzing multiple nitrosamines in diverse pharmaceuticals will be limited or attenuated owing to the chemical properties of target analytes or matrix hinderance of pharmaceutical substrates. To extend the applicability of GC analysis for multiple nitrosamines in pharmaceuticals, this study presented a gas chromatograph tandem mass (GC-MS/MS) method for monitoring 14 nitrosamines within 44 pharmaceuticals, whereas the headspace-solid phase microextraction (HS-SPME) sampling mode was introduced. Chromatographic separation was achieved on a DB-heavyWax column (30 m × 0.25 mm; i.d., 0.25 µm), whereas the HS-SPME sampling mode with a 50/30 µm DVB/CAR/PDMS extracting fiber was applied for comparison of the direct injection mode. Meanwhile, the HS-SPME conditions were optimized to evaluate the effects of the parameters on analyzing total nitrosamines in pharmaceuticals by GC-MS/MS. The optimal conditions of HS-SPME were as follows: extracting solution of 90% NaCl, HS incubation time 1 min, SPME adsorbing at 80 ℃ for 30 min, and desorbing at 250 ℃ for 5 min. The limit of quantification (LOQ) for 14 nitrosamines in pharmaceutical matrices under the optimal conditions was 0.05 μg/g for the optimal HS-SPME, whereas the value was 0.05-0.25 μg/g for direct injection.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.jpba.2022.115003 | DOI Listing |
Int J Cancer
December 2024
Department of Urology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Animal models of N-butyl-N-(4-hydroxy butyl) nitrosamine (BBN)-induced urothelial carcinoma (UC), particularly bladder cancer (BC), have long been established. However, the rare incidence of BBN-induced upper urinary tract UC (UTUC), which originates from the same urothelium as BC, remains elusive. The scarcity of animal models of UTUC has made it challenging to study the biology of UTUC.
View Article and Find Full Text PDFRSC Adv
December 2024
Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University 1-1 Xiangling Road Luzhou Sichuan 646000 People's Republic of China
Protein arginine methyltransferase 5 (PRMT5), an epigenetic target with significant clinical potential, is closely associated with the occurrence and development of a range of tumours and has attracted considerable interest from the pharmaceutical industry and academic research communities. According to incomplete statistics, more than 10 PRMT5 inhibitors for cancer therapy have entered clinical trials in recent years. Among them, the second-generation PRMT5 inhibitors developed based on the synthetic lethal strategy demonstrate considerable clinical application value.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Medicinal and Aromatic Plants Research Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza 12622, Egypt.
Lung cancer is a prevalent and very aggressive sickness that will likely claim 1.8 million lives by 2022, with an estimated 2.2 million additional cases expected worldwide.
View Article and Find Full Text PDFMolecules
December 2024
Faculty of Medicine, The John Paul II Catholic University of Lublin, Konstantynów 1J/4.03, 20-708 Lublin, Poland.
Improved methods for the synthesis of nicotine are of great importance due to the wide range of applications of synthetic nicotine, which is free from contamination with nitrosamines. Herein, we present a four-step chemical synthesis of ()-nicotine, involving the reduction in myosmine, enantiomeric separation of nornicotine, and subsequent methylation of the appropriate enantiomer of nornicotine obtained. The reduction in myosmine was investigated using both electrochemical and chemical approaches, achieving up to 90% yields of pure nornicotine.
View Article and Find Full Text PDFMolecules
November 2024
Laboratory of Pharmaceutical Analysis, Department of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
In recent years, the detection of nitrosamine precursors has become an important issue for regulatory authorities such as the European Medicines Agency (EMA) and the Food and Drug Administration (FDA). The present study provides a pre-column derivatization method for the analysis of dimethylamine (DMA) and diethylamine (DEA) in pharmaceutical products using HPLC and a fluorescence detector. Appropriate chromatographic parameters, including mobile phase composition (organic solvent, buffer, pH), elution type, flow rate, temperature, and λexcitation/emission, were investigated.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!