In Silico Prediction of N-Nitrosamine Formation Pathways of Pharmaceutical Products.

The recent discovery of N-nitrosodimethylamine (NDMA), a mutagenic N-nitrosamine, in pharmaceuticals has adversely impacted the global supply of relevant pharmaceutical products. Contamination by N-nitrosamines diverts resources and time from research and development or pharmaceutical production, representing a bottleneck in drug development. Therefore, predicting the risk of N-nitrosamine contamination is an important step in preventing pharmaceutical contamination by DNA-reactive impurities for the production of high-quality pharmaceuticals.

Comparison of ephedrine and pseudoephedrine contents in 34 Kampo extracts containing Ephedrae Herba used clinically in Japan.

Ephedrae Herba is among the important crude drugs prescribed in Kampo medicine for the treatment of cold, flue, rhinitis, nasal congestion, cough, and asthma. The active ingredients of Ephedrae Herba, ephedrine (E) and pseudoephedrine (PE), are potent sympathomimetic compounds that stimulate α-, β1-, and β2-adrenoceptors resulting in dilatation and alleviation of nasal mucosal hyperemia. Hypertension, palpitations, insomnia, and dysuria are the main adverse effects of E and PE, which can be avoided by determining the actual contents of these alkaloids in Kampo extracts containing Ephedrae Herba.

N-Nitrosodimethylamine (NDMA) Formation from Ranitidine Impurities: Possible Root Causes of the Presence of NDMA in Ranitidine Hydrochloride.

N-Nitrosodimethylamine (NDMA) is a probable human carcinogen. This study investigated the root cause of the presence of NDMA in ranitidine hydrochloride. Forced thermal degradation studies of ranitidine hydrochloride and its inherent impurities (Imps.

A simple and rapid method to simultaneously analyze ciclesonide and its impurities in a ciclesonide metered-dose inhaler using on-line supercritical fluid extraction/supercritical fluid chromatography/quadrupole time-of-flight mass spectrometry.

A simple and rapid on-line SFE/SFC/quadrupole TOF-MS method to simultaneously analyze active pharmaceutical ingredients and impurities from metered-dose inhalers (MDIs) was developed using ciclesonide MDI (CIC-MDI) as an example. CIC-MDI, as drug Alvesco®, has been approved for the treatment of bronchial asthma, and its major impurities are listed in the European Pharmacopoeia and in the supplementary package inserts of Alvesco® (called as "Pharmaceutical interview form" in Japan). In the developed method, CIC-MDI was manually sprayed only once on a glass disc prior to the SFE/SFC/quadrupole TOF-MS.