Analyse des Ammoniumbituminosulfonates Ichthyol®

Koch, J.; Moser, Reinhold; Demel, Johann

doi:10.1002/ardp.19853180303

Cited by 7 publications

(5 citation statements)

References 12 publications

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“…2 sample preparation). However, the limited information on the chemical composition of SBS and matrices similar to the API or its precursor distillate [ 21 – 24 ] hinders a comprehensive quantitative evaluation of these effects. For example, multiple compounds and classes may be present in the API besides sodium sulfonates, like unreacted starting material compounds and organic by-products [ 25 ].…”

Section: Resultsmentioning

confidence: 99%

Applying a risk assessment guided evaluation for verifying comprehensive two-dimensional gas chromatography to analyse complex pharmaceuticals

Schwalb,

Tiemann,

Käfer

et al. 2023

Anal Bioanal Chem

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The reliability of analytical results is critical and indispensable when applied in regulated environments such as the pharmaceutical industry. Therefore, analytical workflows must be validated. However, validation guidelines are often designed for quantitative targeted analysis and rarely apply to qualitative untargeted approaches. In this study, we employ a risk assessment approach to identify critical parameters which might influence the qualitative results derived by online derivatisation — comprehensive two-dimensional gas chromatography coupled to a high-resolution time-of-flight mass spectrometer (GC × GC-HR-ToF–MS) for the analysis of the active pharmaceutical ingredient (API) sodium bituminosulfonate (SBS). To show the complexity and feasibility of such an approach, we focus on investigating three potential risk factors: sample preparation, vapourability, and the thermal stability of sulfonates. Through the individual evaluation of these potential risk factors due to the application of sample preparation approaches and thermal gravimetric analysis (TGA), we demonstrate the high derivatisation efficiency and repeatability of the online derivatisation method and confirm the absence of derivatisation-induced side reactions. In addition, we also show the potential thermal instability of an incompletely derivatised API. To address the limitation of these individual assessments, we applied a holistic evaluation step with negative electrospray ionisation Fourier transform ion cyclotron resonance mass spectrometry (ESI( −) FT-ICR MS) as an orthogonal technique. This confirms that most of the API is detected via the presented GC-based method. Thereby, we demonstrated the practical feasibility of the risk assessment-based approach to ensure the validity of the qualitative data for a complex untargeted method. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

Applying a risk assessment guided evaluation for verifying comprehensive two-dimensional gas chromatography to analyse complex pharmaceuticals

Schwalb,

Tiemann,

Käfer

et al. 2023

Anal Bioanal Chem

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show abstract

“…Besides the mono-sulfonated substance classes, just a small extent of non-sulfonated substance classes were detected. Koch et al [ 11 ] analyzed a comparable matrix using 1D GC but their results are limited to a list of compound classes and their degree of alkylation without chromatographic information. Therefore, a direct comparison was not possible but the high number of peaks, their similar polarity, and size would be unresolvable by a 1D GC.…”

Section: Resultsmentioning

confidence: 99%

“…An additional study from the 1980s investigated the composition of the sulfonated compounds in ABS. In this analysis, sulfonated alkylbenzenes, -thiophenes, and other sulfonated arenes have been detected with a high extent of sample preparation [ 11 ]. Recent studies with state-of-the-art instrumentation targeting the chemical composition of the sulfur-rich distillates or their sulfonated products are missing, which limits further development of the API.…”

Section: Introductionmentioning

confidence: 99%

Analysis of complex drugs by comprehensive two-dimensional gas chromatography and high-resolution mass spectrometry: detailed chemical description of the active pharmaceutical ingredient sodium bituminosulfonate and its process intermediates

et al. 2022

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The European pharmacopeia provides analytical methods for the chemical characterization of active pharmaceutical ingredients (APIs). However, the complexity of some APIs exceeds the limitations of the currently prevailing physicochemical methods. Sodium bituminosulfonate (SBS) is described by the collection of key parameters of generalizing criteria such as dry matter, sulfur and sodium content, and neutrality, but techniques to unravel the complexity on a molecular level are lacking. We present a study based on online derivatization with tetramethylammonium hydroxide in combination with comprehensive two-dimensional gas chromatography coupled to an electron ionization high-resolution time-of-flight mass spectrometer (GC × GC-HR-ToF–MS) for the chemical description of SBS as well as its process intermediates. The application of GC × GC allowed the comprehensive description of the chemical components in the API and the process intermediates for the first time. Furthermore, it was possible to classify peaks regarding their elemental and structural composition based on accurate mass information, elution behavior, and mass fragmentation pattern. This work demonstrates not only the general applicability, advantages but also limitations of GC × GC for the characterization of APIs for complex drugs. Graphical Abstract

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“…Previous studies were able to identify alkylated thiophenes and benzothiophenes in the precursor distillates 23,24 and sulfonated alkylbenzenes, -thiophenes, and other sulfonated arenes in the APIs. 15,25 Challengingly, analytical methodologies for targeting aromatic sulfonates are rarely found in the literature, 26,27 and regulatory solutions for in-depth speciation are entirely missing. Standard spectroscopic techniques are not able to cope with the tremendous complexity and could only be suitable for high-throughput quality control and bulk analysis.…”

Section: Introductionmentioning

confidence: 99%

“…However, chemical speciation along the different processing steps is crucial for understanding transformation processes and ensuring high-quality standards. Previous studies were able to identify alkylated thiophenes and benzothiophenes in the precursor distillates , and sulfonated alkylbenzenes, -thiophenes, and other sulfonated arenes in the APIs. , Challengingly, analytical methodologies for targeting aromatic sulfonates are rarely found in the literature, , and regulatory solutions for in-depth speciation are entirely missing. Standard spectroscopic techniques are not able to cope with the tremendous complexity and could only be suitable for high-throughput quality control and bulk analysis. , Molecular information can be gained by high-performance chromatography combined with mass spectrometry. , However, the development of chromatographic protocols can be tedious and error-prone.…”

Section: Introductionmentioning

confidence: 99%

Rock-to-Pharma: Characterization of Shale Oil-Based Nonbiological Complex Drugs along the Production Process by High-Resolution Mass Spectrometry

Tiemann,

Rüger,

Schwalb

et al. 2024

Anal. Chem.

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Antibiotic resistance has become a primary concern in medicine because of the overuse and misuse of classical pharmaceuticals. Recently, nonbiological complex drugs (NBCDs) have gained interest for their complex pharmacological profiles. Bituminosulfonates, which have lately been tentatively allocated toward NBCDs, are pharmacologically well-studied and show low potential in resistance development. However, molecular composition knowledge is limited. With this work, we present a comprehensive approach to investigate the manufacturing process of complex pharmaceuticals like bituminosulfonates on a molecular level via Fourier-transform ion cyclotron resonance mass spectrometry. The application of various hyphenations and ionization techniques comprehensively covers the entire mass and polarity range of the matrix, and the high sensitivity enables the identification of significant and minor chemical alterations caused by the multistep manufacturing process. The distillation of the shale crude oil eliminates highly aromatic PAH and PASH constituents. ESI(−) revealed strong PAH-and PASH-sulfonate formation after reacting the shale oil distillate with sulfuric acid. Increasing alkylation reduced the sulfonation yield, instead causing oligomerization side reactions, as observed by APPI analysis. Furthermore, multidimensional gas chromatography coupled with highresolution mass spectrometry verified core structural motifs. With this work, we demonstrate the high potential of FT-ICR MS in NBCD process analysis. The results also give valuable information for future pharmacological investigations focusing on specific compound classes or properties.

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Analyse des Ammoniumbituminosulfonates Ichthyol®

Cited by 7 publications

References 12 publications

Applying a risk assessment guided evaluation for verifying comprehensive two-dimensional gas chromatography to analyse complex pharmaceuticals

Applying a risk assessment guided evaluation for verifying comprehensive two-dimensional gas chromatography to analyse complex pharmaceuticals

Analysis of complex drugs by comprehensive two-dimensional gas chromatography and high-resolution mass spectrometry: detailed chemical description of the active pharmaceutical ingredient sodium bituminosulfonate and its process intermediates

Rock-to-Pharma: Characterization of Shale Oil-Based Nonbiological Complex Drugs along the Production Process by High-Resolution Mass Spectrometry

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