Journal of pharmaceutical and biomedical analysis
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J Pharm Biomed Anal · Sep 2019
Simultaneous detection of nitrosamines and other sartan-related impurities in active pharmaceutical ingredients by supercritical fluid chromatography.
Since July 2018, the pharmacological class of "sartans" has been the subject of considerable media and analytical interest, as it became known that they are contaminated with nitrosamines such as N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA) and N-nitrosodiisopropylamine (NDiPA). Previous compendial methods are not able to detect these new contaminants. Using the latest and innovative Quality-by-Design (QbD) approach, it has now been possible to develop an analytical method that enables to investigate sartans, such as valsartan and losartan. ⋯ By using SFC, a broad spectrum of nonpolar and very polar impurities can be separated and analyzed in under 20 min. The analytical method developed is validated for limit testing according to ICH Q2(R1) and fulfills default thresholds of EMA and FDA for testing of drug substances and genotoxic impurities. Additionally, it can also be adapted to other pharmaceuticals that may be contaminated with nitrosamines, since tetrazole synthesis as the underlying cause of nitrosamine contamination is important for a set of other non-sartan drug substances.
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J Pharm Biomed Anal · Sep 2019
Rapid profiling of alkaloid analogues in Sinomenii Caulis by an integrated characterization strategy and quantitative analysis.
Alkaloids, the principal constituents in the caulis of Sinomenium acutum, have gained an increasing interest over the past decades since they are widely employed as a clinical treatment for rheumatoid arthritis. In the present study, an integrated characterization strategy by combining mass defect filtering-based structure classification (MDFSC) and diagnostic fragment-ion-based extension (DFIBE) was firstly proposed for rapid profiling of alkaloids in Sinomenii Caulis (SC) via ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The rectangular MDFSC window could more accurately screen the target alkaloids of different types, and the DFIBE could facilitate the acquisition of characteristic fragment ions for structural elucidation of alkaloids. ⋯ A total of 91 alkaloids, including 82 targeted ones (26 morphinans, 22 aporphines, 20 protoberberines and 14 benzylisoquinolines) were unambiguously identified or tentatively characterized in SC, and 14 of them were reported for the first time. Sinomenine and magnoflorine could be selected as chemical markers to evaluate the quality of SC from different localities. In conclusion, the proposed method provided a potential approach for chemical profiling and holistic quality control of herbal medicines.