Journal of pharmaceutical and biomedical analysis
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J Pharm Biomed Anal · Nov 2020
HS-SPME-GC-MS as an alternative method for NDMA analysis in ranitidine products.
N-nitrosodimethylamine (NDMA) is a carcinogenic contaminant that was accidentally discovered in drugs, such as valsartan and ranitidine, and more recently in metformin. Liquid chromatography tandem mass spectrometry (LC-MS/MS) is the method typically used for the analysis of NDMA in ranitidine. It seems that using gas chromatography (GC) for NDMA analysis is problematic as ranitidine is sensitive to high temperatures. ⋯ Interestingly, using HS-SPME-GC-MS was advantageous because we could avoid the high temperature utilized in the liquid injection and HS modes. Moreover, the results obtained using HS-SPME-GC-MS provided a good match with those achieved using LC-MS/MS. The feasibility of using HS-SPME-GC-MS to successfully analyze NDMA in ranitidine opens new opportunities for the analysis of this contaminant in pharmaceuticals, specifically those that are heat-labile.
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J Pharm Biomed Anal · Sep 2020
Determination of N-nitrosodimethylamine and N-nitrosomethylethylamine in drug substances and products of sartans, metformin and ranitidine by precipitation and solid phase extraction and gas chromatography-tandem mass spectrometry.
N-Nitrosodimethylamine (NDMA) has been detected in some drug substance and drug products containing sartans, ranitidine and metformin. N-nitrosodiethylamine (NDEA) has also been found to be present in some sartan medications. A method for the simultaneous detection of NDMA and NDEA in drug substances and finished products of sartans, metformin and ranitidine has been optimized using isotope dilution, clean-up procedure and gas chromatography-tandem mass spectrometry (GC-MS/MS). ⋯ NDMA was detected with a concentration of 0.004 mg/kg in a valsartan and 0.012 mg/kg in a ranitidine, and NDEA was detected at concentrations of 0.009 and 0.008 mg/kg in irbesartan and rosartan. Otherwise, NDMA was detected at a concentration of 0.062 mg/kg in a fimasartan product and 0.009 mg/kg in a ranitidine product. This method is available for all drug substances and finished products of sartans; metformin and ranitidine.
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J Pharm Biomed Anal · Jul 2020
Simultaneous analysis of saturated and unsaturated oxylipins in 'ex vivo' cultured peripheral blood mononuclear cells and neutrophils.
Oxylipins are a family of saturated and unsaturated fatty acids peroxidation products with bioactive properties. We have developed an improved method for the measurement of ex vivo oxylipin production by peripheral blood mononuclear cells (PBMCs) and neutrophils. We aimed to develop an analytical method to determine the production rates of polyunsaturated fatty acids (PUFAs), PUFA-oxylipin, and saturated-oxylipins by stimulated PBMCs and neutrophils based on solid phase extraction and HPLC-MS/MS technology. ⋯ LPS stimulation decreased 16-hydroxyl-palmitatte (16-OHPAL) production and DHA secretion in neutrophils, while PMA stimulation increased the production rate of AA and its derivate oxylipins, 5-HETE, 15-HETE, and PGE2. In conclusion, we have developed a new method to determine oxylipins derived from both saturated and unsaturated fatty acids in culture cell media. This method has enough sensitivity, and accuracy, to determine oxylipin production and fatty acid secretion by PBMCs and neutrophils.
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J Pharm Biomed Anal · Jul 2020
Rapid identification and pharmacokinetic studies of multiple active alkaloids in rat plasma through UPLC-Q-TOF-MS and UPLC-MS/MS after the oral administration of Zanthoxylum nitidum extract.
Zanthoxylum nitidum (Roxb.) DC. (ZN) belongs to the genus Zanthoxylum of Rutaceae and has various chemical ingredients and pharmacologic effects. Alkaloids are its main active constituents responsible for diverse pharmacologic effects, such as anti-tumor, anti-bacterial, anti-inflammatory, and analgesic activities. The chemical and pharmacological effects of ZN are well reported, but the in vivo pharmacokinetic profiles of its main active alkaloids are poorly investigated. ⋯ The plasma drug concentration of benzophenanthridine alkaloids, such as NIT, CHE, and DHCHE, were still low even after dose differences were deducted. For the furan quinoline alkaloids (such as SKI, FAG, and DIC), only SKI showed high plasma drug concentration, although SKI content comprised only approximately 1/6 of benzophenanthridine alkaloids. This study is the first to simultaneously determine the above-mentioned active alkaloids in rat plasma and would contribute to the comprehensive understanding of in vivo pharmacokinetic behavior on active alkaloids in ZN extract.
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J Pharm Biomed Anal · Feb 2020
Characterization of chemical profile and quantification of representative components of DanLou tablet, a traditional Chinese medicine prescription, by UHPLC-Q/TOF-MS combined with UHPLC-TQ-MS.
DanLou tablet (DLT), a famous traditional Chinese medicine prescription (TCMP) consisting of 10 herbal medicines, is extensively used for the treatment of angina pectoris and acute coronary syndrome in China. However, active chemical constituents responsible for the therapeutic effects still remain unclear, due to the fact that the complex composition in DLT have not been holistically clarified. Therefore, this study aimed to characterize the chemical profile and simultaneously quantify the representative components in DLT. ⋯ Further chemometric analysis indicated that danshensu and salvianolic acid B were the most significant quantitative markers for the content fluctuation of DLT. In summary, the chemical profiles of DLT were systematically characterized and a practical quantitative method combined with chemometrics was developed to evaluate the intrinsic quality of multiple DLT samples in this study. The present work would be helpful for guaranteeing the safety, efficacy, and controllability in clinical medication of DLT.