Electrochemical Flow Injection Analysis of Hydrazine in an Excess of an Active Pharmaceutical Ingredient - Achieving Pharmaceutical Detection Limits Electrochemically
At a Glance
Section titled âAt a Glanceâ| Metadata | Details |
|---|---|
| Publication Date | 2015-08-24 |
| Journal | Analytical Chemistry |
| Authors | Robert B. Channon, Maxim B. Joseph, Eleni Bitziou, Anthony W. T. Bristow, Andrew Ray |
| Institutions | AstraZeneca (United Kingdom), University of Warwick |
| Citations | 57 |
Abstract
Section titled âAbstractâThe quantification of genotoxic impurities (GIs) such as hydrazine (HZ) is of critical importance in the pharmaceutical industry in order to uphold drug safety. HZ is a particularly intractable GI and its detection represents a significant technical challenge. Here, we present, for the first time, the use of electrochemical analysis to achieve the required detection limits by the pharmaceutical industry for the detection of HZ in the presence of a large excess of a common active pharmaceutical ingredient (API), acetaminophen (ACM) which itself is redox active, typical of many APIs. A flow injection analysis approach with electrochemical detection (FIA-EC) is utilized, in conjunction with a coplanar boron doped diamond (BDD) microband electrode, insulated in an insulating diamond platform for durability and integrated into a two piece flow cell. In order to separate the electrochemical signature for HZ such that it is not obscured by that of the ACM (present in excess), the BDD electrode is functionalized with Pt nanoparticles (NPs) to significantly shift the half wave potential for HZ oxidation to less positive potentials. Microstereolithography was used to fabricate flow cells with defined hydrodynamics which minimize dispersion of the analyte and optimize detection sensitivity. Importantly, the Pt NPs were shown to be stable under flow, and a limit of detection of 64.5 nM or 0.274 ppm for HZ with respect to the ACM, present in excess, was achieved. This represents the first electrochemical approach which surpasses the required detection limits set by the pharmaceutical industry for HZ detection in the presence of an API and paves the wave for online analysis and application to other GI and API systems.
Tech Support
Section titled âTech SupportâOriginal Source
Section titled âOriginal SourceâReferences
Section titled âReferencesâ- 2008 - Guidance for Industry. Genotoxic and Carcinogenic Impurities in Drug Substances and Products: Recommended Approaches