Bioanalytics – Chemical
2019 PharmSci 360
Tissue analysis of small molecule drugs and biotherapeutics has become critically important to elucidate their pharmacokinetic (PK) and pharmacodynamic (PD) properties in pharmaceutical research and development.
Several factors should be carefully evaluated and optimized while developing a quantitative method in tissues, e.g. taking a representative sample from a target organ, sensitivity and selectivity, contamination issues, homogenization and extraction recovery. Sensitivity and selectivity represent the most important challenges due to the complexity of biological matrices and because concentrations of these agents in the tissues can be significantly lower than those found in serum.
LC–MS methods are commonly applied for quantification of small molecule drugs and represent a promising solution for the quantification of protein biotherapeutics offering significant advantages over LBAs, including higher selectivity, wider dynamic range and reduced timelines for method development. Prior to method application, an appropriate validation strategy should be adopted based on what decision the concentration data will be supporting.
In this presentation, case studies will be presented, showing how small molecule drugs, biotherapeutics and biomarkers can be quantified in tissues, e.g. in:
1) liquid and solid ocular tissues (e.g. aqueous humor, vitreous humor, tears, cornea, lens) for ophthalmology drugs.
2) tumor tissues from xenograft animal models for oncology drugs.
3) brain and CSF to determine circulation versus tissue penetration effects for CNS active drugs.
4) infected tissues to assess pharmacodynamics of antibiotic drugs.
5) target tissues to assess distribution and toxicity of oligonucleotide drugs, along with their biomarkers of efficacy (e.g. mRNA, downstream proteins) in the same tissue sample for a better PK/PD assessment.