pharmacokinetics

In the last few decades, the hyphenated analytical techniques including liquid chromatography (LC) in combination with a mass spectrometer (MS) i.e., LC/MS, have made a major impact in pharmaceutical drug discovery and development. LC-MS hase been routinely used in pharmaceutical formulation development for drug substance and drug product characterization, molecular weight and fragmentation patterns determination, breakdown studies, and to identify impurities and degradation products. Recent advancements in LC-MS instrumentation, have allowed the technique to be implemented in several indications i.e., cancer, cardiovascular, respiratory, neurological, rare diseases etc. across preclinical (in vitro and in vivo) and clinical projects to evaluate pharmacokinetic and pharmacodynamic factors. LC-MS has overcome the sensitivity and dynamic range challenges to successfully identify and characterize drug molecules to help projects that use small molecules, biologics, and gene and cell therapy/editing platforms as drug modalities. This technique may provide several advantages over other analytical approaches including specificity, multiplexing, precision to quantify drug analyte or a biomarker in a variety of matrices like blood (plasma/serum), tissue, cerebrospinal fluid, urine, cells etc. In this review, we have highlighted LC-MS applications to study pharmaceutical formulations, pharmacokinetics and pharmacodynamics involving small molecule modality.

A simple and rapid liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay method has been developed and validated for simultaneous quantification of two protease inhibitors ritonavir and atazanavir in human plasma. Saquinavir was used as an internal standard. The analytes were extracted from human plasma samples by solid-phase extraction technique using a Orpheus C18 extraction cartridges. The reconstituted samples were chromatographed on a C18 column by using a 85:15 (v/v) mixture of methanol and 5mM ammonium acetate as the mobile phase at a flow rate of 0.9 mL/min. The calibration curves obtained were linear (r ³ 0.99) over the concentration range of 8.0-1600.0 ng/mL for ritonavir and 50.5-5995.2 ng/mL for atazanavir. The results of the intra- and inter-day precision and accuracy studies were well within the acceptable limits. A run time of 2.0 min for each sample made it possible to analyze more than 300 plasma samples per day. The proposed method was found to be applicable to clinical studies.