Quality Control Acceptance Criteria Research Articles

Degradation kinetics and characterization of major degradants of binimetinib employing liquid chromatography-high resolution mass spectrometry

Binimetinib (BMT) has recently been approved by the USFDA for the treatment of melanomas. An extensive literature search revealed that degradation kinetics of BMT is not reported in any scientific report. Till date, no stability indicating analytical method (SIAM) is available for quantification of BMT in presence of its impurities. Moreover, information on degradation products (DPs) of BMT and the degradation pathway is not known. In this study, we have developed a SIAM for BMT and characterized its major DPs using LC-Q-TOF-MS/MS. The SIAM was validated according to the ICH guideline and subsequently used to study the degradation kinetics of BMT. The method was found to be useful for separating BMT and all its DPs formed during different stress conditions. Three new DPs have been identified and characterized. H1 (acid hydrolytic DP) and O1 (oxidative degradation product) were isolated and characterized by NMR (1H) spectroscopy. An in silico toxicity evaluation of the DPs was performed using ProTox-II toxicity prediction software. Data obtained from the degradation kinetic study revealed that BMT degradation follows first-order kinetics under acidic hydrolysis and oxidative stress conditions. The degradation kinetics mechanism and knowledge on the pathway of degradation established through this study can be useful to improve the stability profile of the drug and to propose a more appropriate storage condition. The degradation impurities we have identified and characterized can be useful in setting the quality control acceptance criteria of the drug after their required qualification. The quantitative assay method can be used for routine quality control and stability study analysis of BMT in pharmaceutical industries and research laboratories.

Abstract 4592: Verification of a complete sample to insight liquid biopsy workflow: NGS of ccfDNA from stabilized blood

Abstract Introduction: Analysis of circulating cell-free DNA (ccfDNA) from blood in the fields of life science, clinical research and beyond is expanding and has become widely accepted. The complete workflow entails collection and stabilization of blood, transport, plasma processing, extraction of ccfDNA and downstream analysis. Considering the usual low sample input and required high sensitivity for quality control (QC) and variant detection, optimal outcomes require verification of the entire workflow. In this verification study, human blood was collected, stabilized, and then processed to isolate ccfDNA from plasma using the PAXgene® Blood ccfDNA System for subsequent analysis by next-generation sequencing (NGS). To verify the workflow, several sample QC criteria were assessed at each step of the workflow, including ccfDNA yield, target enrichment, library preparation, target sequencing and analysis. Methods: Blood from 60 healthy consented donors was collected into PAXgene Blood ccfDNA Tubes* and stored for 7 days at room temperature (15–25°C) to simulate a typical processing delay in a routine setting. Automated ccfDNA extraction was performed on the QIAsymphony® SP instrument using the QIAsymphony PAXgene Blood ccfDNA Kit* and protocol. ccfDNA stability after blood storage was confirmed by qPCR. ccfDNA samples were sequenced on the QIAGEN GeneReader® NGS System, including the GeneRead™ QIAact Actionable Insights Tumor (AIT) Panel* for PCR target enrichment, library preparation on the QIAcube® instrument, QC with capillary electrophoresis, sequencing on the GeneReader instrument* and data management with the QIAGEN Clinical Insight (QCI™) Analyze* tool. Results: After blood storage for 7 days, ccfDNA yield was similar to ccfDNA yield observed directly after blood draw. All samples (60/60) passed the required QC criteria after target enrichment (amplicon size around 160 bp) and library preparation (amplicon size around 252 bp and absense of unspecific products <170 bp). Also, all GeneReader NGS acceptance criteria that defined “passed” or “out-of-spec” samples were passed after sequencing, including reads above average quality 25 with 90.16 ± 2.04% (acceptance criteria >80%), region of interest with coverage of bases >500x with 99.83 ± 0.47% (>90%) and region of interest with coverage of bases >200x with 99.99 ± 0.03% (>95%). Across all samples, 17 ± 5 different variants in 7 ± 1 different genes were identified with the AIT targeted panel. Conclusions: NGS is one of the most important applications for analysis of ccfDNA in research and clinical settings. This study verified that ccfDNA stabilized and extracted with the PAXgene Blood ccfDNA System is highly suitable for NGS applications, meeting quality control acceptance criteria for 100% of analyzed samples. *For Research Use Only. Not for use in diagnostic procedures. Citation Format: Tomasz Krenz, Andrea Ullius, Ricardo Huebel, Thorsten Voss, Daniel Groelz, Eric Provencher, Timothy R. Buirkle. Verification of a complete sample to insight liquid biopsy workflow: NGS of ccfDNA from stabilized blood [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4592.

Quantitative profiling of oxylipins in plasma and atherosclerotic plaques of hypercholesterolemic rabbits.

Oxylipins are oxidation products of polyunsaturated fatty acids (PUFAs) that affect a broad range of physiological processes, including cell proliferation, inflammation, inflammation resolution, and vascular function. Moreover, oxylipins are readily detectable in plasma, and certain subsets of oxylipins have been detected in human atherosclerotic lesions. Taken together, we set out to produce a detailed quantitative assessment of plasma and plaque oxylipins in a widely used model of atherosclerosis, to identify potential biomarkers of disease progression. We administered regular chow or regular chow supplemented with 0.5% cholesterol (HC) to male New Zealand white rabbits for 12 weeks to induce hypercholesterolemia and atherosclerosis. Our targeted lipidomic analyses of oxylipins on plaques isolated from rabbits fed the HC diet detected 34 oxylipins, 28 of which were in compliance with our previously established quality control acceptance criteria. The arachidonic acid (AA) metabolite derived from the COX pathway, 6-keto-PGF1α was the most abundant plaque oxylipin, followed by the linoleic acid (LA) metabolites 9-HODE, 13-HODE and 9,12,13-TriHOME and the arachidonic acid (AA)-derivatives 11-HETE and 12-HETE. We additionally found that the most abundant oxylipins in plasma were three of the five most abundant oxylipins in plaque, namely 11-HETE, 13-HODE, and 9-HODE. The studies reported here make the first step towards a comprehensive characterization of oxylipins as potentially translatable biomarkers of atherosclerosis.

Quality Control of EPS External Wall Thermal Insulation System

To ensure the construction quality of EPS external wall thermal insulation system , need to controll raw materials, construction conditions, construction methods and quality control acceptance criteria and other aspects

Implementing PBMS improvements to USEPA's Cryptosporidium and Giardia methods

The US Environmental Protection Agency (USEPA) has developed a new approach for modifying analytical methods—the performance‐based measurement system (PBMS). Methods 1622 and 1623 are the first microbiological methods from USEPA to be based on PBMS. This approach to method validation and implementation allows the methods to be modified to improve performance, increase laboratory efficiency, or reduce costs, provided that the methods' quality control acceptance criteria are met. Although the PBMS approach to method flexibility is straightforward in principle, laboratories and manufacturers need to understand the requirements and process for USEPA evaluation and approval of modified methods before embarking on studies to demonstrate acceptable performance of a modified version of a method. This article describes the process for conducting modified method acceptability studies for USEPA methods 1622 and 1623 and gives examples of both successful and unsuccessful outcomes.

Determination of inorganic anions in environmental waters with a hydroxide-selective column

US Environmental Protection Agency Method 300.0 specifies the use of an IonPac AS4A anion-exchange column with a carbonate–hydrogencarbonate eluent and suppressed conductivity detection for the determination of inorganic anions in environmental waters by ion chromatography. Hydroxide eluents have not typically been used for the routine analysis of common inorganic anions due to the lack of an appropriate hydroxide selective column and the difficulty in preparing contaminant free hydroxide eluents. The use of ion chromatography with a hydroxide-selective IonPac AS17 column, automated eluent generation and potassium hydroxide gradient represents a new approach to the routine determination of inorganic anions in environmental waters. This new approach, which is a modification of Method 300.0, allows equivalent method performance with improved linearity, precision, and method detection limits. The AS17 column provides superior retention of fluoride from the column void volume and improved resolution from small organic acids, such as formate and acetate, compared to the AS4A column. Quantitative recoveries were obtained for all the common inorganic anions spiked into typical environmental waters using this new approach, and the Performance Based Measurement System Tier 1 method validation quality control acceptance criteria are well within the acceptable ranges defined by Method 300.0. In addition, the EG40 eluent generator eliminates the need to manually prepare eluents, increasing the level of automation and ease-of-use of the ion chromatography system.

Precision, accuracy, and data acceptance criteria in biopharmaceutical analysis.

Accuracy and precision are the most important criteria in the assessment of an analytical method, and monitoring quality control during sample analysis is essential to ensure the validity of reported results. Various approaches to testing accuracy, precision, and quality control were applied to 10 analytes from seven chromatographic bioanalytical methods. These methods include fixed interval bias and significance testing for accuracy; fixed interval percentage relative standard deviation (%RSD) and analysis of variance (ANOVA) approaches for precision; +/- 20% fixed range, 99% confidence interval, multiple rules, and range chart for individuals approaches for quality control acceptance criteria. Quality control approaches were also applied to the entire run and to a bracketed approach whereby results are considered valid only if bracketed by acceptable quality control. Accuracy and precision were assessed for six runs of each analyte at three concentrations established to represent the calibration range of the analytical method. Quality control acceptance criteria were evaluated using all data sets from each of the analytical methods collected during the course of running various numbers of real samples. The data suggest that the fixed interval bias criteria for accuracy was a more liberal method of accuracy assessment because three of the seven methods would have been rejected according to the significance testing criteria whereas all were acceptable by the fixed internal bias criteria. Precision can be effectively assessed for between- and within-run data by criteria set on unconfounded %RSD values or by separation of the sources of variation using an ANOVA approach applied to confounded data.(ABSTRACT TRUNCATED AT 250 WORDS)