microsampling for neurodegenerative diseases & CNS drugs: Dr. Michele Protti

Christa Nuber
Oct 2, 2020 7:00:00 AM
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For this episode of the Microsamplify Podcast, we spoke with Michele Protti, PhD, Assistant Professor at the Department of Pharmacy and Biotechnology of the University of Bologna, Italy. Dr. Protti works closely with Prof. Laura Mercolini in the Research Group of Pharmaco-Toxicological Analysis, or PTA Lab. Dr. Protti's research interest is in analyzing central nervous system drugs, metabolites and biomarkers in microsamples and alternative biological matrices. Most recently, Dr. Protti and his colleagues in the Mercolini Lab have been investigating CNS disorders and neurodegenerative disease, specifically methods for testing biomarkers, drugs and metabolites through advanced microsampling approaches.

Neoteryx: Hello Dr. Protti, and welcome to the Microsamplify Podcast from Neoteryx. Thanks for taking the time to speak with us about your work at the University of Bologna.

Dr. Protti: Thank you for the invitation. For me it’s an honor joining other bioanalytical experts on the Microsamplify Podcast by Neoteryx. And, for my research group, this is a great opportunity to share our research and talk about our daily work on the development of innovative methods and the design of novel microsampling strategies.

Neoteryx: Can you tell us a little more about yourself, your research focus, and your role in the PTA Lab at the University of Bologna?

Dr. Protti: I’m currently Assistant Professor at the Department of Pharmacy and Biotechnology of the University of Bologna in Italy. I got my Ph.D. in chemistry in 2006. I’m working in the PTA research group coordinated by Professor Laura Mercolini, where I carry out my research work within a National PRIN2017 project, coordinate the activities of PhD students and undergraduates, and do teaching activities. My research is focused on the development and validation of analytical approaches, mainly based on mass spectrometry for drugs and biomarkers, with special emphasis on sample collection, sample pretreatment and process miniaturization. One of the main goals of the PTA Lab research group is to design methodologies and platforms with high applicability. That’s why we are involved in several collaborative and multidisciplinary projects where the implementation of novel sampling and pretreatment strategies could benefit different areas and applications.

Neoteryx: Your most recent research projects in the PTA Lab are focused on analytical methods for the assessment of CNS drugs and disease biomarkers. Can you give us a summary of these projects and how you are using Mitra® devices with VAMS® microsampling technology for this kind of analysis in blood?

Dr. Protti: Neurodegenerative diseases and related mental disorders represent a complex scenario that has engaged scientists in various areas for years and still needs in-depth studies. These can be aimed at the discovery of early biomarkers of disease progression; at the identification of new therapeutic targets; at the monitoring of concentrations in biological fluids of drugs and their metabolites for optimal personalization of therapies.

At the PTA Lab, we believe that the development of innovative and cutting-edge bioanalytical methods for the study of CNS disorders by monitoring biomarkers and drugs in biological fluids may represent very powerful and very useful tools in all these areas of research and for clinical applications to delicate populations.

Microsampling has a series of intrinsic advantages that, if properly studied and developed, can benefit, expand, speed up and ease several kinds of studies, with benefits for researchers, clinicians and patients.

Neoteryx: How do you think microsampling technologies can impact research aimed at studying the complex mechanisms underlying neurodegenerative diseases? And, how might microsampling impact the monitoring of drugs that are active in the central nervous system?

Dr. Protti: The study of the complex relationships between metabolism and the onset of diseases affecting the central nervous system require in-depth studies often carried out primarily on animals. In this context, microsampling allows a reduction in the volumes of biological samples needed for the analysis, a reduction in the number of animals required in accordance with the principles of the 3Rs, and a reduction in the results variability, with consequent improvement of data quality.

Moreover, the implementation of microsampling approaches to clinical practice would bring solid advantages for both clinicians and patients. Indeed, in the context of pharmacological therapies for the treatment of neurodegenerative diseases and mental disorders, complex polypharmacy regimens are often adopted that must be carefully tailored to the patient in order to personalize the therapies. In fact, narrow therapeutic windows, possible side effects, and potential drug-drug interactions highlight the need to accurately and frequently monitor the plasma levels of drugs and their active metabolites in order to correlate them to therapeutic outcomes and then adjust dosages.

In this scenario, the adoption of feasible, minimally invasive microsampling procedures has great potential to intensify this practice, allowing more frequent sampling and analysis. It also has potential to improve patient compliance, and lead to the refinement of therapeutic regimens, and the complete customization of therapies with the perspective of precision medicine practices.

Neoteryx: How do you foresee the future of diagnostics and clinical practice in the study of and therapy for neurodegenerative diseases and central nervous system disorders?

Dr. Protti: I hope for a progressive increase in the use of microsampling strategies both in research and in clinical practice. On the one hand, bioanalytical research can benefit from the streamlining of procedures and protocols, thus being able to develop high-throughput methodologies with high applicability.

On the other hand, clinicians can obtain fundamental data from patients more frequently, optimize therapies more effectively and more quickly, thus limiting the occurrence of side effects and, in turn, hospitalization rates. This would ensure huge benefits for clinicians, patients and the healthcare system as a whole.

In this framework, bioanalytical scientists have a primary role in the dissemination of these strategies. Further studies are needed, further methods have to be developed proving the effectiveness of these approaches by comparison with classic routine practices. And, information is needed in order to make more people aware of the existence and relevance that these new strategies can have on routine practices.

Neoteryx: The popular term among researchers and clinicians these days is “patient-centric.” When you have explored the use of Mitra® microsampling devices and dried blood spot cards, or DBS cards, in your cannabinoid analysis research, which of the two approaches have you found to be more “patient-centric” or more “user-friendly,” and why?

Dr. Protti: DBS is obviously considered the forerunner of modern microsampling techniques. The features of DBS are now well studied and known, as are the drawbacks and potential issues associated with DBS sampling. This is why there is a need for new strategies that can tackle such issues. When it comes to patient-centric sampling, the holy grail to be achieved is represented by effective home-sampling and self-sampling, where the patient can comfortably and independently collect microsamples by pricking their finger, and easily send them to clinical facilities or analysis laboratories. From this point of view, Mitra with VAMS offers clear advantages, thanks to its ease of use without requiring professional assistance, tools or special training. Obviously, all of this contributes to subject compliance, and offers advantages regarding the frequency with which sampling and analysis can take place, with a consequent improvement in the analytical result itself.

Neoteryx: You and your colleagues recently published a paper about your blood microsampling research. Can you tell us just a bit about the paper, where it is published, and how our listeners can find it or access it?

Dr. Protti: I can think of at least five or six research papers published by our research group on microsampling since the start of 2020. These came out of fruitful collaborations and were focused on the quali-quantitative instrumental analysis in microsamples—not only whole blood, but also deriving from other biological fluids like urine, oral fluid and plasma. We analyzed mainly drugs active on the central nervous system in the context of therapeutic drug monitoring, for example, antipsychotics and antidepressants. And we also analyzed drugs of abuse, such as cocaine and its main metabolites; and substances prohibited in sports, such as anabolic steroids and glucocorticoids, for possible application in sport drug testing.

These research papers are all published in high-profile bioanalytical journals in the hope of giving more relevance to these techniques by demonstrating their reliability and solidity. And, don’t forget the tutorial paper that we published together with our colleagues Professor Laura Mercolini and Professor Roberto Mandrioli on VAMS technique, where we collected all the main and useful information to date from all the research studies involving VAMS, together with protocols and insights for the further development and optimization of this promising technique.

Neoteryx: Thank you, Dr. Protti, for speaking with us about how you apply microsampling in your work in the PTA Lab at the University of Bologna. We wish you and your colleagues great success with your many projects!

And, thanks to our audience for listening to this episode of the Microsamplify Podcast, a partner to The Microsampling Blog from Neoteryx.

Here are links to some of the research papers published by Dr. Protti and his colleagues in the PTA Lab at the University of Bologna:

1. Whole blood and oral fluid microsampling for the monitoring of patients under treatment with antidepressant drugs (2020), https://www.sciencedirect.com/science/article/pii/S073170852031270X

2. Blood and Plasma Volumetric Absorptive Microsampling (VAMS) Coupled to LC-MS/MS for the Forensic Assessment of Cocaine Consumption (2020), https://www.mdpi.com/1420-3049/25/5/1046

3. Dried Urine Microsampling Coupled to Liquid Chromatography—Tandem Mass Spectrometry (LC–MS/MS) for the Analysis of Unconjugated Anabolic Androgenic Steroids (2020), https://www.mdpi.com/1420-3049/25/14/3210

4. Microsampling and LC–MS/MS for antidoping testing of glucocorticoids in urine (2020), https://www.future-science.com/doi/10.4155/bio-2020-0044

5. Assessment of capillary volumetric blood microsampling for the analysis of central nervous system drugs and metabolites (2020), https://pubs.rsc.org/en/content/articlelanding/2020/AN/D0AN01039A

6. Tutorial: Volumetric absorptive microsampling (VAMS) (2019), https://www.sciencedirect.com/science/article/pii/S0003267018310626

7. Determination of oxycodone and its major metabolites in haematic and urinary matrices: Comparison of traditional and miniaturised sampling approaches (2018) https://www.sciencedirect.com/science/article/pii/S0731708517331345

8. Enantioseparation and determination of asenapine in biological fluid micromatrices by HPLC with diode array detection (2018), https://onlinelibrary.wiley.com/doi/full/10.1002/jssc.201701315

9. Dried haematic microsamples and LC–MS/MS for the analysis of natural and synthetic cannabinoids (2017), https://www.sciencedirect.com/science/article/pii/S1570023216306171

10. LC–MS/MS and volumetric absorptive microsampling for quantitative bioanalysis of cathinone analogues in dried urine, plasma and oral fluid samples (2016), https://www.sciencedirect.com/science/article/pii/S0731708516300772

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Research Group of Pharmaco-Toxicological Analysis, or PTA Lab, University of Bologna, Italy

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