Bioanalysis Zone

2015 Young Investigator: Mieke Carlier


Mieke Carlier x150

Nominee: Mieke Carlier, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Belgium

Nominated By: Alain Verstraete, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Belgium


Supporting Comments: The first three and a half years of Mieke’s career performing research in bioanalysis have been extraordinarily productive, with 16 accepted papers, most of them in journals with a high impact factor. She started by developing an analytical method, quickly overcoming all the associated challenges, principally the instability of the target analytes. She also focused on making the method robust and practical to perform, so the results could be obtained quickly, in time for the next dose adjustment. Mieke also focused on the interpretation of the results and pharmacokinetic/pharmacodynamic modeling in order to transform the analytical data into meaningful information. She can work with great autonomy, and has great problem-solving skills. During her research stay in Australia and at international scientific meetings, she has made a lot of useful connections that have resulted in joint publications. She has just submitted her PhD, but has already received several invitations to give talks at other universities and at scientific meetings. She is driven and gets things done in a very timely manner, within budget, and is a very enthusiastic about her work; it is a joy working with her.

What made you choose a career in bioanalysis?

I have known I wanted to be a pharmacist ever since I was little. As soon as I started my studies, and partly influenced by popular TV shows, I discovered the interesting field of clinical chemistry and bioanalysis and realized that I wanted to specialize further in this field. After graduating, I received a fellowship to start a PhD, which convinced me to pursue my dream of doing research. The topic of my PhD appealed to me, and I have never doubted it since, because I believe that optimizing dosing of antibiotics has the potential to improve patients’ outcomes.

Describe the main highlights of your bioanalytical research, and its importance to the bioanalytical community.

For my research we needed a fast assay to determine antibiotic concentrations in the plasma of critically ill patients. For these antibiotics there are currently no automated assays available, so we decided to use liquid chromatography coupled to mass spectrometry, a technique that is already used in our routine practice. The method needed to be a fast with minimal handling in the pre-analytical phase. Therefore we decided to use protein denaturation and subsequent dilution, which is a very easy clean up procedure, using deuterated internal standards. The runtime was only 2.5 minuets per sample. The method has been used at our institution for a couple of years now and we have never had any problems with it. The importance for the community is to show that minimal runtimes can be achieved, and chromatographic separation is not required as long as you have good internal standards.

Describe the most difficult challenge you have encountered in the laboratory and how you overcame it.

The most difficult challenge for me has been the quantitative analysis of another antibiotic, colistin, using LC-MS/MS. The project is very challenging, because colistin is a rather large molecule, which is quite different from the analysis of small molecules. I explored the literature and tried to replicate every method, which had previously been published, but did not get good results. Finally I discovered that colistin was sticking to the PEEK autosampler needle, which is a plastic, and therefore the PEEK needle needed to be replaced with a stainless steel one. What I have learned is that you need to pay attention to every detail, and ask authors questions if they don’t include certain information in their article.

Where do you see your career in bioanalysis taking you?

In my area of research there is still so much not known. We have just started evaluating the concentrations of these antibiotics in plasma but almost nothing is known about the concentrations in other fluids such as; the epithelial lining fluid in the case of a pneumonia, abdominal fluid, muscle tissue, saliva, and so on. I hope to keep working on this and gain much more knowledge with respect to the pharmacokinetics of these drugs in different patient fluids.

How do you envisage the field of bioanalysis evolving in the future?

I hope in the future that automated LC-MS will be a core part of the lab, so that we can offer therapeutic drug monitoring of many compounds for which there is currently no immunoassay available 24/7. It is now possible to measure glucose continuously using a small inserted sensor under the skin. With the advancement of miniaturization technologies microchip-based systems may become available which could measure a whole range of molecules simultaneously.

Please list up to five of your publications in the field of bioanalysis:

1. Carlier M, Stove V, Roberts JA, Van De Velde E, De Waele JJ, Verstraete AG. Quantification of seven β-lactam antibiotics and two β-lactamase inhibitors in human plasma using a validated UPLC-MS/MS method. J. Antimicrob. Agents 40(5), 416—422 (2012).

2. De Waele JJ, Carrette S, Carlier M et al. Therapeutic drug monitoring-based dose optimisation of piperacillin and meropenem: a randomized controlled trial. Intensive Care Med. 40(3), 380—387 (2014).

3. Carlier M, Carrette S, Stove V, Verstraete AG. Does consistent piperacillin dosing result in consistent therapeutic concentrations in critically ill patients? A longitudinal study over an entire antibiotic course. J. Antimicrob. Agents 43(5), 470—473 (2014).

4. Carlier M, De Waele JJ, Verstraete AG, Stove V. Exploration of the Pre-analytical Stability of β-Lactam Antibiotics In Plasma And Blood – Implications For Therapeutic Drug Monitoring and Pharmacokinetic Studies. Clin. Chem. Lab. Med. doi: 10.1515/cclm-2014-0833 (2014) (Epub ahead of print)

5. Carlier M, Stove V, De Waele JJ, Verstraete AG. Ultrafast quantification of β-lactam antibiotics in human plasma using UPLC-MS/MS. J .Chromatogr. B 978-979, 89—94 (2015).

Please select one publication from above that best highlights your career to date in the field of bioanalysis and provide an explanation for your choice.

1. Carlier M, Stove V, De Waele JJ, Verstraete AG. Ultrafast quantification of β-lactam antibiotics in human plasma using UPLC-MS/MS. J Chrom B. 978-979, 89—94 (2015).

Improving throughput is very important for bioanalysis. This publication summarizes the ultra fast method I developed, which now enables easy to perform therapeutic drug monitoring of β-lactam antibiotics at our institution.



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