Drug Testing by LC-MS: Immunosuppressants and Antifungals

Agenda:

1. Analysis of Plasma Mycophenolic Acid for Clinical Research

2. UPLC-MS/MS Analysis of Azole Antifungals in Serum for Clinical Research

Mycophenolic acid is an immunosuppressant agent that acts by inhibiting inosine monophosphate dehydrogenase in the purine synthesis pathway required for the growth of B and T cells. Several existing methods for the analysis of mycophenolic acid lack the ability to separate mycophenolic acid from its metabolites MPAG and AcMPAG. In this presentation we will learn how UPLC-MS/MS is able to chromatographically separate mycophenolic acid from its metabolites in a run time of 3 minutes.

Although microbiological test methods are in use to measure azole antifungals, enhanced activity of the itraconazole metabolite – hydroxyitraconazole – can overestimate concentrations. Similarly, the use of two or more drugs in combination can impair the utility of microbiological test methods. Use of UPLC-MS/MS enables separation of itraconazole and voriconazole from their metabolites, and the selectivity provided by mass selective detection provides a reliable means of analysis of antifungal compounds in serum for clinical research purposes.

Presenter: Stephen Balloch (Senior Scientist, Clinical Applications, Waters UK)

Stephen Balloch graduated from the University of York (UK) with a Masters degree in Chemistry which included a strong focus on analytical chemistry and a year in industry, in which he gained experience in a range of analytical techniques.

His first permanent post was at Charles River Laboratories, a GLP compliant contract research laboratory in Edinburgh, in which he progressed to the role of Study Director and gained further exposure to LC-MS and LC-MS/MS instrumentation, including Waters instruments.

Since 2010, he has been part of the clinical team in the Scientific Operations group in Waters (Wilmslow, UK). His principal focus has been on the development and validation of bioanalytical methods according to CLSI guidelines, with a focus on therapeutic drug monitoring. Additionally, he has supported newborn screening, steroid and vitamin analysis.

Presenter: Gareth Hammond (Principal Scientist, Waters UK)

Gareth Hammond is currently a Principal Scientist, within the Scientific Operations group, at Waters Corporation, Wilmslow, UK. He leads a small team of scientists which perform research and development activities for Waters applications and products in the Health Sciences field. His primary area of expertise is therapeutic drug monitoring and LC-MS/MS Method Development and Validation. He is also supports IVD system product development activities for Waters providing voice of the customer focus.