Biomedical Engineering Reference
In-Depth Information
Challenges and Strategies in Drug Residue Measurement
(Bioanalysis) of Ocular Tissues
Poonam R. Velagaleti and Michael H. Buonarati
Abstract
Bioanalysis (quantification of drug/metabolite residue in biological fluids and tissues) plays an important
role in support of drug efficacy and safety studies during drug development. Bioanalysis can be very
challenging when the drug or the metabolites to be measured are unstable or are difficult to extract from
biological matrices or when significant matrix interference is experienced during detection of the analytes of
interest. Ocular tissue bioanalysis is particularly challenging because of the anatomical complexity of the
eye. Furthermore, several heterogeneous tissues of the eye such as conjunctiva, sclera, cornea, and retina
may act as barriers to drug absorption and distribution within the eye and therefore each ocular tissue must
be collected individually and analyzed to determine drug and metabolite concentrations. Many ophthalmic
drugs are administered topically and less than 5 % of the applied drug is likely to penetrate the eye. Most of
the topically applied drug may be washed away by tears, cleared by other mechanisms, and/or absorbed into
the systemic circulation. Because of the limited bioavailability, the drugs may not always reach targeted
therapeutic concentrations in the ocular tissue(s). Without sensitive and accurate bioanalytical methods to
measure and demonstrate that drug concentrations within the ocular tissues reach appropriate levels,
following drug administration, erroneous conclusions may be drawn regarding efficacy and/or local safety.
Pharmacokinetic measurements in blood/plasma for assessing systemic bioavailability, or residence time
and drug distribution, are generally not useful in ocular studies since systemic exposure may not be directly
related to exposure in the tissues of the eye after local ocular routes of administration. Systemic exposure,
nonetheless, is very important in evaluating drug safety. Limited availability of control matrices needed for
ocular bioanalysis studies poses additional challenges that may be partially addressed by using surrogate
matrices. This chapter discusses the unique challenges and their resolution during eye tissue collection,
method development, and the conduct of sample analysis for ocular bioanalytical studies.
Key words
Ocular bioanalysis, Ocular tissues, Eye dissection, Tissue homogenization, Drug
extraction, Drug analysis, Surrogate matrix
1
Introduction
Drug exposure assessment, systemic and/or at the site of action, in
human or animal studies is a vital part of drug development. This
allows correlations of drug-mediated biological responses to time
of exposure (pharmacokinetics) that relate both to the desirable
therapeutic effect and to undesirable adverse responses (toxicity)
to the administered drugs. Measurement of drugs and their
metabolites in biological matrices in typical bioanalytical studies
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