RESUMO
An analytical method has been developed for trace analysis (i.e. sub-ppm levels) of a key synthetic impurity, 14W80 ((Z)-2-(2,3-dichlorophenyl)-2-(guanidinylimino)acetonitrile) in lamotrigine (3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine). 14W80 is isobaric with lamotrigine, which gives an extra layer of complexity to its determination and the various problems associated with development of an appropriate methodology are discussed in this work. Ultimately, a liquid chromatography tandem mass spectrometry (LC-MS/MS) method using in-source fragmentation with Atmospheric Pressure Chemical Ionisation (APCI) followed by multiple reaction monitoring (MRM) has been found to provide adequate sensitivity and specificity. A detection limit of 25 ppb mass fraction relative to lamotrigine was achieved for 14W80. The use of solid phase extraction (SPE) enhanced the detection limit to 2 ppb mass fraction relative to lamotrigine.
Assuntos
Anticonvulsivantes/análise , Cromatografia Líquida/métodos , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Triazinas/análise , Acetonitrilas/análise , Acetonitrilas/química , Anticonvulsivantes/síntese química , Anticonvulsivantes/química , Contaminação de Medicamentos/prevenção & controle , Lamotrigina , Estrutura Molecular , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Comprimidos/química , Triazinas/síntese química , Triazinas/químicaRESUMO
A reversed-phase high-performance liquid chromatography/electrospray ionisation mass spectrometry (HPLC/ESI-MS) method has been developed to conclusively differentiate the epimers betamethasone and dexamethasone and various esterification products (betamethasone and dexamethasone 21-acetate, betamethasone and dexamethasone 21-phosphate, betamethasone 17-valerate, betamethasone 21-valerate and betamethasone 17,21-dipropionate) in counterfeit drugs. Good separation with baseline resolution of all epimers or isomers was obtained on a Zorbax Eclipse XDB or Luna C8 column, using a step gradient with mobile phases of 0.05 M ammonium acetate and acetonitrile. Betamethasones can also be distinguished by the relative abundance of their m/z 279 ion in the positive electrospray tandem mass spectra. The LC/MS or LC/MS/MS method developed was successfully applied to the analysis of drug product samples, i.e. creams and tablets.