Spotlight on BioAnalytical Method Development
Bioanalytical method development plays a vital role in the drug development process, helping to detect and quantify the levels of drugs and metabolites in biological systems (or matrices). In bioanalytical terms, method development is the creation of the analytical process for identifying and quantifying known components present in a biological sample matrix. Analyte components are measured by several methods and it involves many considerations such as chemical properties of the analyte, concentration levels, sample matrix, cost of the analysis, speed of the analysis, quantitative or qualitative measurement. The process of method development includes sampling, sample preparation, separation, detection, and evaluation of the results.1
The role of a bioanalytical method development team is simple: to produce accurate and precise methods that work every time for our analysts. Achieving a perfect method each time would be ideal, however we know that it may not always be a possibility. So, our approach at Quotient is to focus on producing good quality methods that analysts can quickly deploy, for either a short preclinical study of a hundred samples or for a major clinical study of twenty thousand, enabling us to do our part in helping get molecules to patients faster.
When developing bioanalytical methods, , we work in two different capacities with our customers. Methods can be transferred in from an outside laboratory, which is the quickest route. Or methods can be produced from scratch, which is harder because there isn’t a pre-existing method to work from. However, creating a method from scratch allows our team to use our skills more freely and deploy innovative techniques or new equipment, which can often lead to a better quality method or faster analyses.
Our team possesses a broad range of experience in chemical synthesis, batch quality analysis and biological biomarker analysis which we are able to leverage on each project. We believe that a good method developer needs to have a solid scientific skillset, with strong interests in analytical technology & techniques, and a certain ability to be painstaking. While a lot of the work is solitary like pipetting standards, tuning the system, running samples, etc…, it is equally important to be a team player. We need to effectively communicate our progress to the Study Director and often the client directly, we also need to check in with other colleagues when needed for scientific advice or support. And at the end, we must support the analysts as they begin to run the method, because often even the best methods develop issues that simply were not seen in development, such as a matrix effect for example.
The bioanalytical techniques available at Quotient’s Alnwick facility cover the spectrum of analysis, from elemental and small molecule analysis through to large proteins, using principally mass spectrometry. If a customer requires a new bioanalytical method ,we will ask to review and discuss the compound structure, a Certificate of Analysis, the sample matrix, level of validation required and any requirement around detection limits, otherwise we will target our standard limit of quantitation of 1ng/mL in plasma. If a method has to be ready for a specific study start date, then that will also need to be provided for planning purposes. Whatever the method, whether elemental or a protein, and whatever the matrix, we apply the same basic workflow and steps to the project, to ensure everything has gone through the same steps, and by doing so, we are more likely to generate a robust method. This workflow is reproduced at our facility and is shown on the following page. Our major output, or piece de resistance, is the Bioanalytical Specification document, or BAS, which is the full working method and contains all essential data for reproducing the method. We also provide our clients with summary documentation that outlines the key features and decision points for the method. So far, we have produced over 400 bioanalytical methods, in an array of sample matrices. The most common matrix is plasma for circulating active drug; frequently we look at tissues for compounds and particularly elemental analysis, and sometimes faeces.
At Quotient Sciences, we help our customers develop a clearer understanding of what is happening to their molecule as it progresses through the body. Our bioanalytical team has over 40+ years of experience in supporting all stages of drug development from early preclinical through to First-in-Human and subsequent patient trials. Our focus is helping our customers get life changing medicines to patients quickly and efficiently. For more information about our bioanalytical capabilities, click here: https://www.quotientsciences.com/bioanalysis/
1. Kirthi A, Shanmugam R, Shanti Prathyusha M, Jamal Basha D. A Review on bioanalytical method development and validation by RP – HPLC. 2014; 5(4):2265- 2271.2.