Recent application of analytical methods to phase I and phase II drugs development: a review

Abstract

Drug development is a time-consuming and costly process. It is usually divided into four phases, although it is not always possible to draw a sharp line between the various stages. In phase I and II there are many molecules investigate and it is necessary to analyze all of them in a short period of time, with lower costs, and with high-throughput assay. During phase I relevant chemical-physical parameters like the acid dissociation constant, lipophilicity, solubility and stability must be analyzed. Classic techniques such as 'shake-flask' can be used, but instrumental analytical methods such as HPLC may be helpful to improve and enhance the productivity and reproducibility of the results. During phase II the activity of a drug and factors that may have an influence on it, like metabolic profile and transformations, impurities and plasma biding proteins, must be considered. In this field, recent hyphenated analytical methods, such as LC-MS/MS, GC-MS/MS or more complex couplings, can provide more complete information. The aim of this review is to report the processes required for the validation of drug efficacy with reference to the description of 'classic' and modern techniques used.

Lyophilized Biologics

“…For the successful introduction of biopharmaceuticals in the past two to three decades, advancement in stability indicating analytical methods has been instrumental in delivering good quality protein pharmaceuticals with excellent stability profiles [1,12,14,23,26].…”

Stability study of Prulifloxacin and Ulifloxacin in human plasma by HPLC–DAD

“…This problem is especially related to the different physicochemical properties often present between the parent drug and its active metabolite [24][25][26][27][28][29] . SPE has been a usual and generally adopted pre-treatment method for biological samples, suitable for most compounds, with a large variety of physicochemical properties and very effective in the removing the protein, salt and fat of the biological matrix.…”

“…. Following our research, activity focused on drug analyses and characterization [24][25][26][27][28][29] , we report in the present study the development of a simple, rapid and sensitive HPLC method suitable for routine analysis of Prulifloxacin and its related active metabolite in human plasma that can be applied to stability testing and pharmacological trials.…”

HPLC-ESI-IT-MS/MS Analysis and Biological Activity of Triterpene Glycosides from the Colombian Marine Sponge Ectyoplasia ferox

“…This fraction contains glycoconjugates with pharmaceutical potential, owing to its poor hemolytic activity, which is the most common side effect for this class of substances as well as being a considerable obstacle for clinical trials progress [12,13]. …”