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Groningen, Netherlands

It is commonly acknowledged that random and systematic analytical errors contribute to poor data quality, and moreover, to imprecise and inaccurate pharmacokinetic parameters. To investigate the random errors in GLP bioanalysis, common ground has been found in today's bioanalysis to assess the reproducibility of the method by reanalyzing part of the incurred samples. The undesired systematic errors in bioanalysis affecting the trueness of the method and leading to inaccurate data remain relatively unattended so far. In order to obtain both precise and accurate data it is suggested in this paper to apply standard addition experiments to calculate the relative systematic errors as an estimate for the incurred sample accuracy. This approach, which can be seen as an important extension to current guidelines in GLP bioanalysis, is illustrated by assessing the accuracy of the bioanalytical results for a bioequivalence study for alendronate. Source

Wieling J.,QPS Netherlands
Bioanalysis | Year: 2015

Efficient method transfer is the key in advancing drug candidates through development and requires careful planning and communication between the two laboratories. Successful transfers require robust bioanalytical methods that allow for some small deviations from the method in sender laboratory; however, by keeping the fundamentals of the sender method intact. The equivalence of data produced at both sides should be tested by mutually prepared and analyzed QCs and by analyzing incurred samples at both sides and assessed by a statistical equivalence testing. Current regulatory bodies' guidances provide very limited direction for experimental setup and evaluation of transfer. This perspective paper gives an overview of the available approaches and proposes a way forward for the bioanalytical community. © 2015 Future Science Ltd. Source

de Boer T.,QPS Netherlands | Meulman E.,QPS Netherlands | Meijering H.,QPS Netherlands | Wieling J.,QPS Netherlands | And 2 more authors.
Biomedical Chromatography | Year: 2012

To support the evaluation of the pharmacokinetic parameters of asenapine (ASE) in urine, we developed and validated online solid-phase extraction high-performance liquid chromatography methods with tandem mass spectrometry detection (SPE-LC-MS/MS) for the quantification of ASE and two of its major metabolites, N-desmethylasenapine (DMA) and asenapine-N+-glucuronide (ASG). The linearity in human urine was found acceptable for quantification in a concentration range of 0.500-100ng/mL for ASE and DMA and 10.0-3000ng/mL for ASG, respectively. © 2012 John Wiley & Sons, Ltd. Source

de Boer T.,QPS Netherlands | Wieling J.,QPS Netherlands | Meulman E.,QPS Netherlands | Reuvers M.,QPS Netherlands | And 5 more authors.
Biomedical Chromatography | Year: 2011

An early clinical development study (phase I) was conducted to determine the usefulness of dried blood spot (DBS) sampling as an alternative to venous sampling for phenotyping and genotyping of CYP450 enzymes in healthy volunteers. Midazolam (MDZ) was used as a substrate for phenotyping CYP3A4 activity; the concentrations of MDZ and its main metabolite 1'-hydroxymidazolam (1-OH MDZ) were compared between the DBS method from finger punctures, plasma and whole blood (WB), drawn by venipuncture, whereby several methodological parameters were studied (i.e. punch width, amount of dots analyzed and storage time stability). Genotyping between DBS and venous WB samples was compared for CYP2D6 (*3, *4, *6), CYP2C19 (*2, *3), CYP3A4 (*1B) and CYP3A5 (*3C). In addition, the subject's and phlebotomist's satisfaction with venous blood sampling compared with the DBS method was evaluated using a standardized questionnaire. An LC-MS/MS method for the quantification of the MDZ and 1-OH MDZ concentrations in DBS samples was developed and validated in the range of 0.100-100ng/mL. No compromises were made for the limits of quantification of the DBS-LC-MS/MS method vs the authentic plasma and WB methods. © 2011 John Wiley & Sons, Ltd. Source

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