Evaluation of the use of LC-MS in supporting stability studies for preclinical study formulations

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 32; no. 6; pp. 1113 - 1122
• Main Authors: Simmonds, Emma L, Lough, W.John, Gray, Martin R
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 21.08.2003; Elsevier Science
• Subjects: Analytical biochemistry: general aspects, technics, instrumentation; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Chromatography, High Pressure Liquid - methods; Fundamental and applied biological sciences. Psychology; GLP; Liquid chromatography-mass spectrometry; Mass Spectrometry - methods; Pharmaceutical Preparations - analysis; Preclinical study formulations; Sensitivity and Specificity; Spectrophotometry, Ultraviolet; Stability studies; Stable isotope labelled internal standards; Stable isotope labelled internal standards; GLP; Preclinical study formulations; Liquid chromatography-mass spectrometry; Stability studies; Evaluation; Stability; Use; HPLC chromatography; Preclinical trial; Research and development; Mass; Type; Ultraviolet detector; Analysis method; Formulation; Work; Feasibility; Detection; Mass spectrometry
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/S0731-7085(03)00219-X

Assessing the short-term stability of drug development candidates in one or more formulations to be used during their preclinical evaluation is a routine, but important, task. Typically, this is based on data generated by HPLC with ultraviolet detection of the species of interest and using methodology specifically developed and validated for the purpose. This work describes a feasibility study conducted into the use of HPLC with mass spectroscopic detection for work of this type. Experimental details and the results of trials with three different drugs, each in a different vehicle, are given. It was concluded that, by using mass spectroscopic detection, a well-defined strategy could be used to generate stability data, which offered advantages in terms of specificity, speed and sensitivity over that typically used.