Applicability of gas chromatography/quadrupole‐Orbitrap mass spectrometry in support of pharmaceutical research and development

Baldwin, Stephen A.; Bristow, Tony; Ray, Andrew; Rome, Karen; Sanderson, Natalie; Sims, Martin; Cojocariu, Cristian; Silcock, Paul

doi:10.1002/rcm.7505

Cited by 17 publications

(13 citation statements)

References 17 publications

(20 reference statements)

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“…It allows the analytes to condense into a tight band on the head of the column. The split valve will be opened after the split time to flush the injection of any residual specimen [39]. Another injection method that is beneficial to eliminate injector or column contamination is used this is called headspace injection.…”

Section: Gc-msmentioning

confidence: 99%

A Review on Analytical Challenges in Monitoring and Controlling Genotoxic Impurities

Sutnga¹,

R²

2020

Asian J Pharm Clin Res

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Genotoxic impurities (GIs) are chemical agents that have a DNA-interaction characteristic which can ultimately lead to cancer. Their presence in various drug substances had driven various regulatory authorities to guide monitor, control, and to limit their level in various drug products. The objective of this article is to review the analytical approaches and challenges faced while accessing, monitoring, and controlling GIs in pharmaceuticals and also a brief explanation such as low limits of GIs, matrix interference, non-volatility, and environmental conditions encountered during the analysis of GIs are also discussed in this paper. At present, several modern analytical techniques are being used for the analysis of GIs such as high-performance liquid chromatography, liquid chromatography-mass spectrometry, and gas chromatography-mass spectroscopy that have high selectivity and sensitivity, but at the same time, many researchers have reported several challenges while using these techniques. Impacts of GIs are very important and various international organizations such as the World Health Organization have set out rules for regulating these chemicals. Hence, we can conclude that analytical approaches and their challenges are essential to understand because they play a key role to develop robust analytical methods.

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Section: Gc-msmentioning

confidence: 99%

A Review on Analytical Challenges in Monitoring and Controlling Genotoxic Impurities

Sutnga¹,

R²

2020

Asian J Pharm Clin Res

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“…On the other hand, the developments in Atmospheric Pressure Gas Chromatography (APGC) [59] and the recent introduction of an GCcompatible orbitrap mass analyzer seem to turn this trend. The second was already applied in a pharmaceutical setting beyond determination of residual solvents [60]. The combination of these new instruments with the advantage of electron ionization (EI) and concurrent spectral library searching has the potential to introduce a paradigm shift in the choice of MS inlet system (LC versus GC).…”

Section: Technological Advancements Facilitating Data Acquisitionmentioning

confidence: 99%

Mass spectrometry-based structure elucidation of small molecule impurities and degradation products in pharmaceutical development

Liu

Romijn

Verniest

et al. 2019

TrAC Trends in Analytical Chemistry

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Mass spectrometry (MS) has played a critical role in the identification of unknown small molecules for many years. As such, it is also a pivotal technique in the structure elucidation of drug impurities and degradation products during pharmaceutical development. In this review we discuss the regulatory expectations and some general practices regarding the identification of process-related impurities and degradation products of small molecule therapeutics; with an emphasis on the role of MS in this process. Recent advances in instrumentation, facilitating MS-based structure elucidation are covered. Over the last few years, many software tools have been developed that aid in the annotation and identification of small molecules by their precursor and product ion spectra. This evolution is promising since it is key to alleviate the current data interpretation bottleneck. The main approaches used in these bioinformatics tools are critically surveyed. This review aims to give meaningful insight in the current state of MS-based structure elucidation of small molecule impurities and degradation products.

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“…Hence, the use of GC-MS for targeted and non-targeted metabolic studies, especially for breathomics, is highly suitable and powerful [ 15 ]. In recent years, GC-HRMS has gained popularity [ 16 ]. GC-Orbitrap provides a high mass resolving power (120,000 full width at half maximum (FWHM) at ( m / z 200)) combined with a high mass accuracy (<5 ppm), which is needed to avoid isobaric interference [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

pyAIR—A New Software Tool for Breathomics Applications—Searching for Markers in TD-GC-HRMS Analysis

et al. 2022

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Volatile metabolites in exhaled air have promising potential as diagnostic biomarkers. However, the combination of low mass, similar chemical composition, and low concentrations introduces the challenge of sorting the data to identify markers of value. In this paper, we report the development of pyAIR, a software tool for searching for volatile organic compounds (VOCs) markers in multi-group datasets, tailored for Thermal-Desorption Gas-Chromatography High Resolution Mass-Spectrometry (TD-GC-HRMS) output. pyAIR aligns the compounds between samples by spectral similarity coupled with retention times (RT), and statistically compares the groups for compounds that differ by intensity. This workflow was successfully tested and evaluated on gaseous samples spiked with 27 model VOCs at six concentrations, divided into three groups, down to 0.3 nL/L. All analytes were correctly detected and aligned. More than 80% were found to be significant markers with a p-value < 0.05; several were classified as possibly significant markers (p-value < 0.1), while a few were removed due to background level. In all group comparisons, low rates of false markers were found. These results showed the potential of pyAIR in the field of trace-level breathomics, with the capability to differentially examine several groups, such as stages of illness.

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Applicability of gas chromatography/quadrupole‐Orbitrap mass spectrometry in support of pharmaceutical research and development

Cited by 17 publications

References 17 publications

A Review on Analytical Challenges in Monitoring and Controlling Genotoxic Impurities

A Review on Analytical Challenges in Monitoring and Controlling Genotoxic Impurities

Mass spectrometry-based structure elucidation of small molecule impurities and degradation products in pharmaceutical development

pyAIR—A New Software Tool for Breathomics Applications—Searching for Markers in TD-GC-HRMS Analysis

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