HS-GC-FID method for quantification of HFA-152a in cell culture media, and plasma from a range of species and regulatory compliant validations

IF 1.3 4区 医学 Q4 PHARMACOLOGY & PHARMACY Journal of pharmacological and toxicological methods Pub Date : 2023-07-01 DOI:10.1016/j.vascn.2023.107271
Philip J. Kuehl , Stuart Corr , Jabari Farrar , Jacob D. McDonald , Tim Wermer , Derek Weber , Chet Leach
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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.

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HS-GC-FID方法用于定量细胞培养基中的HFA-152a,以及来自一系列物种的血浆和符合监管的验证
引言1,1-二氟乙烷(HFA-152a)正被开发为加压计量吸入器的替代推进剂。作为调节发展途径的一部分,已经对吸入HFA-152a进行了药理学、毒理学和临床研究。这些研究需要符合目的的监管(GxP验证)方法来定量血液中的HFA-152a。方法由于HFA-152a是一种在标准温度和压力下的气体,因此开发了新的方法来支持监管备案所需的广泛物种和浓度的分析。结果所开发的方法利用顶空自动采样器与气相色谱(GC)相结合,进行火焰离子化检测。成功方法的关键因素包括将适用于头部空间小瓶的方法、基质(血液)的体积、物种/研究目标所需的检测范围、将血液处理/转移到头部空间小瓶以及分析样本所需的稳定性/储存。物种特异性测定在小鼠、大鼠、兔、犬和人的调节(GLP)条件下以及豚鼠和细胞培养基的非调节(非GLP)验证下得到了充分验证。讨论总体而言,全血头部空间分析的新方法允许开发和验证用于生成毒代动力学数据的分析方法,这些数据支持HFA-152a作为一种新型pMDI推进剂的临床测试。
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来源期刊
Journal of pharmacological and toxicological methods
Journal of pharmacological and toxicological methods PHARMACOLOGY & PHARMACY-TOXICOLOGY
CiteScore
3.60
自引率
10.50%
发文量
56
审稿时长
26 days
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.
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