Clinical Trials Essentials: The Challenges Scientists Encounter When Conducting LCMS Method Development

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The drug development process is a complex endeavor. Irrespective of the type of pharmaceutical company, each of them faces several challenges. A pharmaceutical company may aim to develop a new drug before anyone else to reap the benefits of patent protection. On the other hand, a contract research organization will focus on providing reliable services to its clientele and drive projects to success. One sure way to achieve success in a drug development scenario is to invest in innovative technologies and achieve and exceed organizational goals. LC-MS method is one such robust bioanalytical technique.

Liquid chromatography-mass spectrometry is one of the most commonly employed bioanalytical techniques in drug research and development. Besides, the alternative of hyphenated techniques has further helped scientists generate more accurate and reliable data, enabling crucial decision-making in the drug development process. However, with any modern and sophisticated technology, there are challenges. It is the same for LC-MS analysis. Hence, the current article highlights the challenges scientists encounter in LC-MS and LC-MS/MS method development in preclinical and clinical drug development.

Challenges in LC-MS and LC-MS/MS method development

LC-MS Method has gained universal acceptance for sensitive and selective detection of analytes in complex biological matrices. However, developing LC-MS and LC-MS/MS methods has inherent complications. A laboratory must ensure that the developed LC-MS method meets all regulatory requirements. Additionally, they must ensure that the bioanalytical method fulfills all business goals of effective and efficient data production.

Bioanalytical scientists must consider all essential parameters while developing an LC-MS method. For example, biological samples consist of numerous matrices such as serum, plasma, tissues, and urine. These samples are innately complex. Besides, each of these samples requires a cleaning process to account for interferences present in them.

Bioanalysis involves testing a large number of study samples. Additionally, each of these samples will consist of multiple target analytes. Hence, it is difficult to prove method suitability in a high throughput environment.

Drug development studies are time-intensive. Hence, acquiring rapid results is the key to accelerating drug development timelines. Researchers have to balance fast analysis against other considerations. However, automated processes have helped researchers achieve short turnaround times.

As mentioned earlier, more target analytes increase the complexity of bioanalysis. This increase in complexity further increases the challenges faced while separating analytes and optimizing the assay. Moreover, achieving the required level of sensitivity becomes crucial during method development, especially for analytes present at low levels.

However, making crucial decisions in the method development process can help scientists counter some of these challenges. Knowing the stage at which samples are collected can help scientists modify method development requirements. For example, study samples from first-in-human studies will require higher resolution than throughput. This difference is because the number of study samples at this stage will be much lesser, and the focus will be on assessing the compound of interest.

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Similarly, in phase III/IV clinical studies, adequate data about the compound of interest is available. Hence, in these clinical trial phases, LC-MS method development will be focused on enhancing analytical efficiency to assess thousands of study samples.