Philip J. Kuehl , Stuart Corr , Jabari Farrar , Jacob D. McDonald , Tim Wermer , Derek Weber , Chet Leach
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引用次数: 0
Abstract
Introduction
1,1-Difluoroethane (HFA-152a) is being developed as an alternative propellant in pressurized metered dose inhalers (pMDIs). As a part of the regulatory development pathway, pharmacology, toxicology and clinical studies have been conducted with inhaled HFA-152a. These studies require fit for purpose regulatory compliant (GxP validated) methods for quantification of HFA-152a from blood.
Methods
As HFA-152a is a gas at standard temperature and pressure, novel methods were developed to support the analysis across the wide range of species and concentrations required for regulatory filing.
Results
The developed methods utilized a headspace auto sampler coupled to a gas chromatograph (GC) with flame ionization detection. Key factors in the successful method included bringing together fit for purpose approaches to the head space vials, volume of matrix (blood), detection range required for species/study objective, handling / transfer of blood into head space vials and the stability/storage required for the analysis of the samples. The species-specific assays were fully validated under regulatory (GLP) conditions for mouse, rat, rabbit, canine and human and non-regulatory (non GLP) validations for guinea pig and cell culture media.
Discussion
Overall the novel approach of head space analysis of whole blood allowed for the development and validation of assays used to generate the toxicokinetic data that supported clinical testing of HFA-152a as a new pMDI propellant.
期刊介绍:
Journal of Pharmacological and Toxicological Methods publishes original articles on current methods of investigation used in pharmacology and toxicology. Pharmacology and toxicology are defined in the broadest sense, referring to actions of drugs and chemicals on all living systems. With its international editorial board and noted contributors, Journal of Pharmacological and Toxicological Methods is the leading journal devoted exclusively to experimental procedures used by pharmacologists and toxicologists.