Lc-Ms/Ms-Based Small Molecule Pk Assay During Preclinical Studies And Clinical Trials

In the past few years, the LC-MS/MS-based bioanalytical techniques have evolved rapidly, creating a larger impact on the new pharmaceutical development. Continuous improvements introduced across both the mass spectral analysis and interface technologies have been purposely combined with the advanced versions of the liquid chromatographic separation techniques. This improvement has transformed how the small molecule pharmacokinetic clinical trials were being performed earlier. Such tools are increasingly employed in analyzing pharmaceutical compounds across a wide stage of both the drug discovery and development processes. These include product characterization, drug discovery, impurity identification, metabolism studies, identification of the degradation products, etc.

Small molecule bioanalysis –

The process of small molecule bioanalysis is defined as a chemical analysis of the pharmaceutical compounds present within a biological matrix. The small molecules are traditional pharmaceuticals typically carrying a low molecular weight below 900 Daltons, which is essential for regulating a biological process. As soon as the drug circulates through the drug development process, it is subjected through various preclinical and clinical studies where the drug is analyzed using a biological matrix, either plasma or serum.

LC-MS/MS bioanalysis –

Liquid chromatography, coupled with tandem mass spectrometry, is now emerging as a popular bioanalytical tool to be used throughout the process of drug discovery and development. This technique relies on the mechanism of charged ions fragmentation and the subsequent detection of their resulting fragments. Thus, it displays a higher selectivity and sensitivity than its previous version of LC-MS in the elucidation of the metabolite structure. Both are hyphenated techniques resulted from the combination of the physico-chemical separation of the liquid chromatography with the mass analysis capability of the Mass Spectrometry. The prime advantage of the LC-MS/MS technique is its higher sensitivity as well as selectivity. These techniques are more beneficially applicable across the clinical laboratories in the processes related to the multiplexing and screen typing assays.

This technique has several advantages. It is relatively easier to achieve the assay selectivity by subjecting the analyte to three different separation stages – sample extraction, column chromatography, and tandem mass spectra detection techniques. The LC-MS/MS bioanalysis's key focus across the pharmaceutical industry is to provide the bioanalytical quantification of the active pharmaceutical drug or its metabolites. This enables the accurate assessment of several bioanalytical parameters such as pharmacokinetics (Pk), bioequivalence (BE), bioavailability (BA), exposure-response relationships, Toxicokinetics (Tk), Pharmacokinetics (PK), etc.

Thus, LC-MS/MS mediated bioanalysis has become the central tool across every drug discovery and development stages of the pharmaceutical industry. In fact, this is a powerful analytical tool for the quantification of the PK assay due to both its higher sensitivity and selectivity. Yet, it is more prone to matrix effects. Other common challenges associated with the LC-MS/MS mediated bioanalysis include low recovery rate, ion suppression, complex sample matrix, inconsistent results, ion enhancement, limited sample volume, low sensitivity, sample throughput, interfering peaks, etc.

Right from the processes related to drug discovery and development to food analysis to environmental monitoring, the LC-MS/MS analysis has proved its efficacy over a broader analytical perspective.

Maria Brown is a medical expert who blog on patient safety and drug efficacy. She’s working for a top medical equipment company. Maria Brown has granted a large online following for herself as an expert medical thought leader.