Modern drug discovery and development is a long, expensive and risky process. To help reduce the cost and risk developing new drugs, pharmaceutical companies are emphasising the use of pharmacokinetic and pharmacodynamic (PK/PD) studies earlier in the preclinical phase. This is leading to bottlenecks in sample analysis, a problem that can be addressed at least in part with better high-throughput sample handling strategies.

PK/PD analysis provides drug developers with valuable information with respect to the overall time course of wanted and unwanted effects of administered drug. A key aspect of this data, generated in exposure studies, is that it enables the correlation of drug effects to the determined concentrations, and not just the administered dose. This is clearly very useful information to have prior to the initiation of clinical trials, but is causing an increase in sample load from the growing number of preclinical PK/PD studies. One particular challenge in the analysis of these samples, usually by atmospheric pressure ionization (API) liquid chromatography/tandem mass spectrometry (LC/MS/MS) instruments, is that there are often large differences in drug concentration between individual samples.

To address these challenges, a group of investigators from AstraZeneca R&D in Södertälje, Sweden, recently developed a combined approach for the high-throughput preparation and analysis of plasma samples for exposure studies using LC/MS/MS. Publishing their results in recent issue of Rapid Communications in Mass Spectrometry, the group used a Tecan Genesis liquid handling system to carry out automated plasma sample preparation, including serial dilutions and other liquid handling steps. This combination of automated liquid handling and a fast LC/MS/MS method increased the overall throughput by three-fold, without comprimising testing accuracy and precision. This report illustrates the potential for high-throughput liquid handling to have a clear impact on the efficiency of drug exposure studies, provided the instrumentation in question is well-integrated into the analytical process.

Article by Briemet al. on HT liquid handling solution for exposure study, Rapid
Communications in Mass Spectrometry, 2007

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