NDMA Formation Due to Active Ingredient Degradation and Nitrite Traces in Drug Product.

N-nitrosamines are genotoxic compounds which can be found as impurities in drug substances and drug products used in the pharmaceutical industry. To date, several possible nitrosamine sources in drug products have been reported and this study aims to illuminate another one. A case of afatinib drug product was investigated, in which up to 50 ppb N-nitrosodimethylamine (NDMA) traces were detected.

Nitrocellulose blister material as a source of N-nitrosamine contamination of pharmaceutical drug products.

The recent focus of pharmaceutical regulatory authorities has been oriented towards the mitigation of carcinogenic N-nitrosamines in drug products and different sources of N-nitrosamines have been revealed. Within this work, the elucidation of a further source of N-nitrosamines in drug products is reported. A case was investigated where traces of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) were detected in a finished dosage form, whereas they were not found in the bulk drug product.

Forced degradation of tacrolimus and the development of a UHPLC method for impurities determination.

An ultra-high performance liquid chromatography method for simultaneous determination of tacrolimus impurities in pharmaceutical dosage forms has been developed. Appropriate chromatographic separation was achieved on a BEH C18 column using gradient elution with a total run time of 14 min. The method was applied to analyses of commercial samples and was validated in terms of linearity, precision, accuracy, sensitivity and specificity.

Solid state compatibility study and characterization of a novel degradation product of tacrolimus in formulation.

Tacrolimus is macrolide drug that is widely used as a potent immunosuppressant. In the present work compatibility testing was conducted on physical mixtures of tacrolimus with excipients and on compatibility mixtures prepared by the simulation of manufacturing process used for the final drug product preparation. Increase in one major degradation product was detected in the presence of magnesium stearate based upon UHPLC analysis.

Isolation and structure determination of oxidative degradation products of atorvastatin.

Methods were developed for the preparation and isolation of four oxidative degradation products of atorvastatin. ATV-FX1 was prepared in the alkaline acetonitrile solution of atorvastatin with the addition of hydrogen peroxide. The exposition of aqueous acetonitrile solution of atorvastatin to sunlight for several hours followed by the alkalization of the solution with potassium hydroxide to pH 8-9 gave ATV-FXA.

Identification of gentamicin impurities by liquid chromatography tandem mass spectrometry.

An HPLC/MS/MS method was developed for identification of impurities in gentamicin. The HPLC was performed on a Synergy Hydro-RP column using 50 mM trifluoroacetic acid (TFA), pH 2 adjusted with ammonium solution and methanol as mobile phase. All impurities in gentamicin were separated from main gentamicin components.

Fast analysis of pravastatin in production media.

High throughput methods (high performance liquid chromatography and capillary electrophoresis) were developed to determine pravastatin in production media. The analyses were performed on particle column, monolithic column and silica capillary filled with borate buffer pH 9.3 containing 20 mM SDS.

Evaluation of the enantiomeric resolution of 7,8-dihydroxy-7,8-dihydrobenzo[a]-pyrene and its 6-fluoro and 6-bromo derivatives on polysaccharide-derived stationary phases.

The enantiomeric resolution and the elution order of (+/-)-trans-7,8-dihydrodiols of benzo[a]pyrene and its 6-fluoro and 6-bromo derivatives were analyzed on three polysaccharide-based columns: Daicel Chiralcel CA-I (cellulose triacetate), OF, and OG [cellulose tris(4-chloro- and 4-methylphenylcarbamate)]. For comparison, the separation of (+/-)-1,1'-bi-2-naphthol was evaluated on the OG and OF columns. Possibly similar interactions of (S)-1,1'-bi-2-naphthol and (7S,8S)-isomers of 6-halo-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene with the chiral sorbent are suggested.