Bioanalysis Zone

An author’s perspective: Amanda King-Ahmad on quantitation of the peptide-1 receptor agonist liraglutide

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To help provide insight into the recent article published in Bioanalysis: A sensitive method for the quantitation of the peptide-based glucagon-like peptide-1 receptor agonist liraglutide in plasma using microfluidics chromatography tandem MS, we spoke with author Amanda King-Ahmad, Senior Scientist at Pfizer (CT, USA). Amanda explains why she felt this was an important area for bioanalysis and worthy of publication.

Amanda King-Ahmad“I am currently a Senior Scientist in Pfizer’s non-regulated bioanalytical group within the Medicine Design-ADME Sciences group, located in Connecticut, USA. Prior to joining Pfizer, I worked as an onsite-contractor at Bristol Myers-Squibb in both New Jersey and Connecticut. I earned my Bachelor’s degree in chemistry and biology from the University of Vermont (VT, USA), and a Master’s degree in cell and molecular biology from Quinnipiac University (CT, USA).

I have worked in the field of bioanalysis for 15 years. I began my career supporting high-throughput metabolic stability and caco-2 permeability screens with LC–MS/MS assays. In 2007, I joined Pfizer’s bioanalytical group to support the small molecule cardiovascular and metabolic disease portfolio. Over the years, the group and my role have evolved to support the entire Pfizer portfolio and the scope of analysis has expanded to include more complex analytes, such as peptides and biomarkers. The majority of the work we do still relies on LC–MS/MS platforms, however, we are always looking to evolve and expand our bioanalytical capabilities and incorporate new technologies into our labs. Over the years we have incorporated supercritical fluid chromatography (SFC), microflow-LC and high-resolution mass spectrometry (HRMS) platforms, which we leverage to overcome bioanalytical challenges presented in the portfolio.”

1. What inspired you to work in this field of bioanalysis?
I have always had a strong interest in medicine and healthcare and have a deep love of science. Personally, I’ve seen family and friends cope with and manage conditions such as diabetes, endocrine disorders, cancer and congenital defects and have witnessed how these effect not only the patient but also those close to them. As a result of these experiences, I was interested in working in the pharmaceutical industry where I could contribute to the development of new medicines to treat patients and improve their lives. I have found that with my role in the bioanalytical group, I am challenged scientifically, have opportunities to learn and grow each day and contribute directly to the development of new efficacious medicines which improve patients’ lives.

2. What impact would you like to see/expect to see as a result of your publication?
First, my hope is that the disclosure of our LC–MS/MS liraglutide method will lead to the faster development of new therapies for Type-2 diabetes mellitus, positively impacting patients’ lives. I also hope that the publication will influence the bioanalytical community to look at alternatives to typical LC–MS/MS assays to address bioanalytical challenges. In undertaking the work for this publication, we would not have been able to meet the Lower Limit of Quantification (LLOQ) desired with conventional flow LC–MS/MS.  However, by taking advantage of the gains in sensitivity seen with reducing the flow rates to sub 10uL/min, we were able to develop this assay with an LLOQ sufficient to cover the average human plasma concentration of liraglutide at the efficacious dose.

3. What are the next steps for your research and this field of bioanalysis?
We are interested in coupling microflow-LC with HRMS and have done some work in this area. The combination of increased sensitivity from microflow-LC along with high resolution mass detection in the full-scan mode provides options for post-acquisition data mining for metabolites, degradants and possible assay trouble shooting.

4. Are there any researchers/projects/technologies that you are watching at the moment, and any you think we should be keeping an eye on?
We are currently doing more with HRMS than we have in the past and I think this will be an up and coming area of bioanalysis to watch. The wealth of information generated from a single sample with HRMS is staggering. Collecting HRMS data on everything in a sample also allows for post-acquisition data mining for things such as metabolites or biomarkers, and other things you might not even be interested in until long after the samples are disposed of. In contrast, with traditional Multiple Reaction Monitoring (MRM) methods, all of this information is lost.

Personally, I am also interested in seeing more multiplexing of assays and I see HRMS as a viable path to this. For example, generating PK and PD data from a single injection would not only be cost and time effective but could also eliminate the PK/PD disconnect that is sometimes observed when these endpoints are generated in different laboratories or with different assays. By combining the assays and multiplexing, we are also reducing the use of animals and are able to collect optimum blood volumes.

5. Do you have any advice for anyone who may be interested in working in this field?
I have been successful in my career in part by taking advantage of every opportunity and making the most of it. In the pharmaceutical industry, the portfolio drives the science and there are very few opportunities to delve into something not related to driving the portfolio.  My advice for those entering the field would be to take every opportunity available to learn and expand your knowledge – don’t limit yourself to what you think you want to do. There are learning opportunities in every situation and from every colleague. Have the mindset to learn as much as possible from every opportunity which arises.

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Reference: King-Ahmad AJ, Kalgutkar AS, Niosi M et al. A sensitive method for the quantitation of the peptide-based glucagon-like peptide-1 receptor agonist liraglutide in plasma using microfluidics chromatography tandem MS. Bioanalysis. 10(5): 357–368 (2018)

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