Centre for Drug Candidate Optimisation - Disciplines

Bioanalysis

LC-MS and LC-MS/MS instrumentation

Rapid, specific and quantitative analysis of drug candidates in biological samples supports all aspects of lead optimisation at the Centre. LC-MS and LC-MS/MS offer the flexibility to develop rapid and specific methods for the analysis of candidate drugs and their metabolites in complex biological matrices.

The Centre is very well equipped with state of the art LC-MS and LC-MS/MS instrumentation to support lead optimisation and pre-clinical studies. All HPLC and UPLC systems are equipped with plate-based sampling compatibility to enable high throughput sample preparation and processing.

Current equipment includes:

• single quadrupole mass spectrometers, which are well suited for samples requiring high specificity in a complex matrix, rapid throughput and moderate sensitivity
• triple quadrupole mass spectrometers that provide high specificity and sensitivity, enabling the detection of trace levels of compounds in complex biological matrices; this instrument is used primarily for quantitative analysis of plasma samples from pharmacokinetic studies
• Time-Of-Flight (TOF) mass spectrometers which provide highly accurate mass determination, particularly suited for identification of metabolites resulting from in vitro and in vivo biotransformation reactions.

In addition to these LC-MS instruments, a number of conventional HPLC systems with a range of detection methods (UV, fluorescence and radiometric) are also available. Other instruments include UV-visible, infra-red, fluorescence and circular dichroism spectrophotometers and nephelometric and fluorescence plate readers.

Analysis of biological samples

Biological samples such as plasma and urine contain multiple components with characteristics similar to the drug or metabolite of interest. The challenge of a bioanalytical method is to detect, identify and quantify the compounds of interest without having to rely on complex sample preparation procedures prior to analysis.

The high specificity of the Centre’s LC-MS instrumentation means that minimal sample preparation is required. Combining this feature with the use of short, narrow-bore analytical columns and generic gradient conditions minimises the time required for assay development and sample run times.