To help provide insight into the recent article published in Bioanalysis: Using miniature MS system with automatic blood sampler for preclinical pharmacokinetics study, we spoke with author Zheng Ouyang, Professor at Tsinghua University (Beijing, China). Zheng explains why he felt this was an important area for bioanalysis and worthy of publication. His work focuses on emerging technologies and miniature mass spectrometry.
“I graduated in 1995 from Tsinghua University (Beijing, China) with a BSc and MSc in engineering, specifically automatic control. I then switched my focus to chemistry and received an MSc in physical chemistry, before starting my career in analytical chemistry. I started as a PhD student, then research scientist and faculty member at Purdue University (IN, USA), working in analytical chemistry and biomedical engineering. I have recently moved back to Tsinghua University, serving as the Chairman of the Department of Precision Instruments, and the Associate Dean for the School of Mechanical Engineering. My research is focused on the instrumentation development for mass spectrometry and applications for biomedical analysis.”
1. Describe some of the challenges of DMPK and the bioanalysis of small molecules?
Drug analysis for DMPK studies is well developed with LC–MS as the major technology platform but is limited as blood samples collected at preclinical or clinical sites have to be sent to external analytical laboratories. Therefore the turnaround time from sample collection to receiving results is relatively long. Also, the sample volume required for the analysis is relatively large so clinical studies involve a large number of mice or rats.
2. Could you list/describe the key factors that need to be considered when introducing a new, emerging technology for preclinical analysis?
A small mass spectrometry analytical system with simple operation protocol should be provided to biologists, nurses or physicians to perform blood sample analyses themselves, obtaining results on-site and in real time. The system itself should be small enough to fit in the lab or clinical room and require minimal maintenance. The entire analytical process, from taking the sample to getting results, should be simple without requiring the skills of a well-trained analytical chemist. We are aiming to meet the demand for clinical applications through the development of miniature mass spectrometry systems. Ambient ionization of the sample has been developed to enable direct sampling and ionization for MS analysis, bypassing the traditional laborious sample preparation that is typically required for LC–MS analysis.
You can find more content on emerging technologies: DMPK and bioanalysis of small molecules on our Spotlight page.
3. What are the advantages/disadvantages of using a miniature mass spectrometer with an automatic blood sampler?
The integration of the miniature MS system with the automatic blood sampler will lead to a complete solution for the preclinical studies. The PK data will be automatically collected with minimal stress experienced by the animals. Using the ambient sampling technologies like the paper spray or slug flow microextraction, ultra-small amounts of samples were taken for analysis.
4. What further advances do you envisage with miniature mass spectrometry in the future?
Not only should the miniature MS systems be used for preclinical study, but also for clinical studies, operated by nurses and physicians. Also, the readily available analyses are expected to be used for guiding therapeutic and other medical procedures. Personalized drug dosage could be determined with the real-time analysis of the individual drug metabolism level and surgery decisions could be facilitated by phenotyping the tumors with the fast analysis of the biopsy tissue samples using miniature MS systems.
Reference: Pu F, Zhang W, Bateman KP, Liu Y, Helmy R and Ouyang Z. Using miniature MS system with automatic blood sampler for preclinical pharmacokinetics study. Bioanalysis: 9(21): 1633-1641 (2017)