Hyphenated liquid chromatography - diode array detection - charged aerosol detection - high resolution - multistage mass spectrometry with online hydrogen/deuterium exchange: One stop solution for pharmaceutical impurity profiling

Thakkar, Harsh; Jain, Shraddha; Kumar, Sandeep; Bhalekar, Vijay S; Gangakhedkar, Shriya; Shah, Ravi P.

doi:10.1016/j.chroma.2022.463725

Cited by 2 publications

(1 citation statement)

References 17 publications

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“…CAD‐based analysis measures all analytes in the sample irrespective of conjugation and chromophoric nature which is on the other hand primary requirement of PDA‐based analysis. It is well known that CAD‐based detection gives a linear/proportionate response for an analyte when the organic composition remains isocratic throughout the analysis [22, 23]. Thus, an inverse gradient CAD‐based approach using dual pump module was employed to achieve a linear response.…”

Section: Methodsmentioning

confidence: 99%

Investigational Study of Mesalamine Dissolution Discrepancy: Utilization of Hyphenated Ultrahigh Performance Liquid Chromatography‐Charged Aerosol Detection‐High‐Resolution Mass Spectrometry

Kumar,

Vakkala,

Ganesan

et al. 2024

Separation Science Plus

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Pentasa (mesalamine/MSLM) is a widely prescribed delayed‐release capsule formulation for the treatment of inflammatory bowel disease. During dissolution study of Pentasa through ultraviolet (UV) spectroscopy, an unusual end‐release of about 110% has been observed. Initial liquid chromatography‐UV (LC‐UV) analyses of these dissolution samples confirmed three prominent peaks other than MSLM with a significant area percentage. Further systematic investigation was carried out by incubating active pharmaceutical ingredient in dissolution media for a longer duration and at elevated temperature followed by analysis through an inverse gradient LC‐charged aerosol detector (CAD). LC–high‐resolution mass spectrometry (HRMS) and online hydrogen‐deuterium exchange (HDX) mass spectrometry were also employed to identify and characterize these artifact products. The area % of prominent artifacts in LC‐UV was found to be way significant when compared to the area % obtained through inverse LC‐CAD, as CAD quantifies the peaks independent of the UV wavelength of absorbance. Inverse LC‐CAD was suitable to determine the relative response factor, whereas LC‐HRMS/MS and online HDX‐MS supported the characterization of these artifacts. These artifacts were found to be trimers, tetramers of MSLM formed due to polymerization, imparting additional pi‐bonds resulting in high UV absorptivity. These techniques when used in combinations serve complimentary to each other during such investigations.

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Section: Methodsmentioning

confidence: 99%

Investigational Study of Mesalamine Dissolution Discrepancy: Utilization of Hyphenated Ultrahigh Performance Liquid Chromatography‐Charged Aerosol Detection‐High‐Resolution Mass Spectrometry

Kumar,

Vakkala,

Ganesan

et al. 2024

Separation Science Plus

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Application of the Different Analytical Methods for Non-chromophoric Pharmaceutical Compounds

Singh,

Pannu,

Singh

et al. 2023

CPA

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The physicochemical properties of non-chromophoric compounds that lack a group to absorb UV-visible radiation make them difficult to analyze with a simple detector. Pharmaceutical formulations and their unknown impurities, which show weak or no response with a UV detector, remain undetected and pose a challenge to the analysis of these compounds. Direct measurement of a chromophore complex formed between the compound and the colored ions present in the electrolyte solution with UV detection is one of the validated methods to analyze non-chromophoric compounds. The derivatization with either chromophore or fluorescent group for the detection of the non-chromophoric compounds with HPLC-UV-Vis or fluorescence detector is also commonly used to study the physicochemical properties of the pharmaceutical formulations. The other techniques to analyze such non-chromophoric compounds include conductivity (ionic molecules), amperometry (molecules oxidized or reduced), mass spectrometry, evaporative light scattering detector (ELSD), condensation nucleation light scattering detector (CNLSD), capillary electrophoresis (CE), gas chromatography (GC), etc. This review covers various separation and detection techniques developed for the analysis of non-chromophoric compounds.

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Hyphenated liquid chromatography - diode array detection - charged aerosol detection - high resolution - multistage mass spectrometry with online hydrogen/deuterium exchange: One stop solution for pharmaceutical impurity profiling

Cited by 2 publications

References 17 publications

Investigational Study of Mesalamine Dissolution Discrepancy: Utilization of Hyphenated Ultrahigh Performance Liquid Chromatography‐Charged Aerosol Detection‐High‐Resolution Mass Spectrometry

Investigational Study of Mesalamine Dissolution Discrepancy: Utilization of Hyphenated Ultrahigh Performance Liquid Chromatography‐Charged Aerosol Detection‐High‐Resolution Mass Spectrometry

Application of the Different Analytical Methods for Non-chromophoric Pharmaceutical Compounds

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