RESUMEN
The 2013 7th Workshop on Recent Issues in Bioanalysis was held in Long Beach, California, USA, where close to 500 professionals from pharmaceutical and biopharmaceutical companies, CROs and regulatory agencies convened to discuss current topics of interest in bioanalysis. These 'hot' topics, which covered both small and large molecules, were the starting point for fruitful exchanges of knowledge, and sharing of ideas among speakers, panelists and attendees. The discussions led to specific recommendations pertinent to bioanalytical science. Such as the previous editions, this 2013 White Paper addresses important bioanalytical issues and provides practical answers to the topics presented, discussed and agreed upon by the global bioanalytical community attending the 7th Workshop on Recent Issues in Bioanalysis.
Asunto(s)
Descubrimiento de Drogas/métodos , Animales , Bioquímica/métodos , Bioquímica/normas , Biomarcadores Farmacológicos/análisis , California , Técnicas de Química Analítica/métodos , Técnicas de Química Analítica/normas , Aprobación de Drogas/métodos , Descubrimiento de Drogas/normas , Humanos , Farmacocinética , Estudios de Validación como AsuntoRESUMEN
BACKGROUND: Matrix effects are one of the major drawbacks of ESI-MS/MS. It is majorly caused by lipids in plasma, which can be overcome by using different extraction techniques. RESULTS: In this investigation, a major matrix effect was observed in samples containing a co-administered drug. Unknown compounds appeared over time in the human plasma samples spiked with co-administered drug creating major ion suppression. The changes in matrix integrity were associated with the organic solvent content in the plasma samples. CONCLUSION: The amount and type of organic solvent added to human plasma along with the storage conditions must be carefully determined during method development in order not to impact quantitation.
Asunto(s)
Cromatografía Líquida de Alta Presión , Compuestos Orgánicos/química , Preparaciones Farmacéuticas/sangre , Solventes/química , Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta Presión/normas , Humanos , Lípidos/química , Morfina/sangre , Derivados de la Morfina/sangre , Naltrexona/química , Control de Calidad , Estándares de Referencia , Espectrometría de Masas en Tándem/normasRESUMEN
Over 400 professionals representing pharmaceutical companies, CROs, and multiple regulatory agencies participated in the 6th Workshop on Recent Issues in Bioanalysis (WRIB). Like the previous sessions, this event was in the format of a practical, focused, highly interactive and informative workshop aiming for high-quality, improved regulatory compliance and scientific excellence. Numerous 'hot' topics in bioanalysis of both small and large molecules were shared and discussed, leading to consensus and recommendations among panelists and attendees representing the bioanalytical community. The major outcome of this year's workshop was the noticeable alignment of multiple bioanalytical guidance/guidelines from different regulatory agencies. This represents a concrete step forward in the global harmonization of bioanalytical activities. The present 2012 White Paper acts as a practical and useful reference document that provides key information and solutions on several topics and issues in the constantly evolving world of bioanalysis.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Guías como Asunto , Inmunoensayo/métodos , Espectrometría de Masas/métodos , Preparaciones Farmacéuticas/análisis , Proteínas Recombinantes/análisis , Calibración , Cromatografía Líquida de Alta Presión/normas , Pruebas con Sangre Seca/métodos , Industria Farmacéutica , Regulación Gubernamental , Humanos , Inmunoensayo/normas , Espectrometría de Masas/normas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estudios de Validación como AsuntoRESUMEN
BACKGROUND: Reanalysis of incurred samples showed that the bioanalytical method for the quantification of ramipril and ramiprilat was generating irreproducible results for ramiprilat. RESULTS: An additional peak interfering with ramiprilat was observed in the incurred samples but not in the calibrant and quality control samples. A similar interference was detected for ramipril, but it was chromatographically separated. Interferences were produced during sample preparation, which involves strong cation exchanger cartridges. The interfering products corresponded to the methylation of ramipril and ramiprilat glucuronide. CONCLUSION: Following this discovery, a reproducible method was developed and successfully validated for ramipril and ramiprilat. Additional stability tests were performed in the presence of glucuronide and diketopiperazine metabolites of ramipril and ramiprilat to demonstrate the method specificity.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/sangre , Artefactos , Dicetopiperazinas/sangre , Glucurónidos/sangre , Ramipril/análogos & derivados , Ramipril/sangre , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Calibración/normas , Enfermedades Cardiovasculares/tratamiento farmacológico , Cromatografía Líquida de Alta Presión , Cromatografía por Intercambio Iónico , Guías como Asunto , Humanos , Espectrometría de Masas , Metilación , Ramipril/uso terapéutico , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Manejo de Especímenes/normas , Estudios de Validación como AsuntoRESUMEN
BACKGROUND: Recently, incurred sample reanalysis (ISR) has become a requirement in bioanalysis. The general guidance recommends investigating ISR failure to evaluate the suitability of an analytical method. In the case of acceptable ISR evaluation, there were no precise recommendations for further testing when sporadic values were obtained. RESULTS: The ISR evaluation performed during a bioequivalence study for the anticonvulsant drug oxcarbazepine showed acceptable ISR results, but one particular chromatographic anomaly led to a thorough investigation. The finding of these tests showed that an oxcarbazepine phase II metabolite occasionally co-eluted with the drug and impacted oxcarbazepine's quantitation through in-source conversion. CONCLUSION: This paper demonstrates the necessity of rigorous interpretation of ISR results and close monitoring of all subject sample results.
