ABSTRACT
The 9th GCCClosed Forum was held just prior to the 2015 Workshop on Recent Issues in Bioanalysis (WRIB) in Miami, FL, USA on 13 April 2015. In attendance were 58 senior-level participants, from eight countries, representing 38 CRO companies offering bioanalytical services. The objective of this meeting was for CRO bioanalytical representatives to meet and discuss scientific and regulatory issues specific to bioanalysis. The issues selected at this year's closed forum include CAPA, biosimilars, preclinical method validation, endogenous biomarkers, whole blood stability, and ELNs. A summary of the industry's best practices and the conclusions from the discussion of these topics is included in this meeting report.
Subject(s)
Biomarkers/analysis , Biosimilar Pharmaceuticals/analysis , Drug Evaluation, Preclinical/methods , Biomarkers/blood , Electronic Health Records , Laboratories , Societies, Medical , Validation Studies as TopicABSTRACT
"The Global CRO Council (GCC) for Bioanalysis was formed in an effort to bring together many CRO leaders to openly discuss bioanalysis and the regulatory challenges unique to the outsourcing industry"
Subject(s)
Biopharmaceutics/standards , Chemistry Techniques, Analytical/standards , Reference Standards , Chemistry Techniques, Analytical/methods , Drug Stability , International Cooperation , Quality ControlABSTRACT
To support clinical development, a liquid chromatographic-tandem mass spectrometric (LC-MS-MS) method was developed and validated for the determination of desloratadine (descarboethoxyloratadine) and 3-OH desloratadine (3-hydroxydescarboethoxyloratadine) concentrations in human plasma. The method consisted of automated 96-well solid-phase extraction for sample preparation and liquid chromatography/turbo ionspray tandem mass spectrometry for analysis. [2H(4)]Desloratadine and [2H(4)]3-OH desloratadine were used as internal standards (I.S.). A quadratic regression (weighted 1/concentration(2)) gave the best fit for calibration curves over the concentration range of 25-10000 pg/ml for both desloratadine and 3-OH desloratadine. There was no interference from endogenous components in the blank plasma tested. The accuracy (%bias) at the lower limit of quantitation (LLOQ) was -12.8 and +3.4% for desloratadine and 3-OH desloratadine, respectively. The precision (%CV) for samples at the LLOQ was 15.1 and 10.9% for desloratadine and 3-OH desloratadine, respectively. For quality control samples at 75, 1000 and 7500 pg/ml, the between run %CV was =7.5% for desloratadine and =6.3% for 3-OH desloratadine. Between run %bias ranged from 4.1 to 8.0% for desloratadine and -11.5 to -4.8% for 3-OH desloratadine. Desloratadine and 3-OH desloratadine were stable in human plasma for 401 days at -22 degrees C, after five freeze/thaw cycles, up to 24 h at room temperature, and in reconstituted sample extracts (up to 185 h at 5 degrees C). This LC-MS-MS method for the determination of desloratadine and 3-OH desloratadine in human plasma met regulatory requirements for selectivity, sensitivity, goodness of fit, precision, accuracy and stability.