ABSTRACT
The cleaning verification of pharmaceutical manufacturing equipment prior to further use is a cGMP requirement. Typically, relevant data are generated by HPLC with UV detection using methods individually developed and validated for each product. This work describes the use of HPLC with mass spectrometry to analyse cleaning verification samples, a novel means of utilising this analytical technology. The initial aim was to produce a single, generic method capable of quantifying a broad range of pharmaceuticals. Ultimately, however, a more effective strategy, in terms of efficiency and reliability, proved to be application of a well-defined approach to the rapid generation of compound specific methods. Results of studies to optimise the sample preparation for a basic compound in drug development (compound 1), together with experimental results for two further compounds are presented. These demonstrated that the combination of a well defined approach to chromatographic method development and mass spectrometric detection provided methodology with advantages in terms of sensitivity. Additionally, and by virtue of its potential for general applicability, the approach proposed has the potential to improve the overall efficiency with which methods for cleaning verification samples can be developed and applied.
Subject(s)
Pharmaceutical Preparations/analysis , Chromatography, High Pressure Liquid , Drug Industry/standards , Indicators and Reagents , Mass Spectrometry , Particle Size , Reproducibility of Results , Spectrophotometry, UltravioletABSTRACT
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.
