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

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: [Figure not available: see fulltext.

Integrated land and water-borne geophysical surveys shed light on the sudden drying of large karst lakes in southern Mexico

Karst water resources play an important role in drinking water supply but are highly vulnerable to even slight changes in climate. Thus, solid and spatially dense geological information is needed to model the response of karst hydrological systems to such changes. Additionally, environmental information archived in lake sediments can be used to understand past climate effects on karst water systems. In the present study, we carry out a multi-methodological geophysical survey to investigate the geological situation and sedimentary infill of two karst lakes (Metzabok and Tzibaná) of the Lacandon Forest in Chiapas, southern Mexico. Both lakes present large seasonal lake-level fluctuations and experienced an unusually sudden and strong lake-level decline in the first half of 2019, leaving Lake Metzabok (maximum depth ∼25 m) completely dry and Lake Tzibaná (depth ∼70 m) with a water level decreased by approx. 15 m. Before this event, during a lake-level high stand in March 2018, we collected water-borne seismic data with a sub-bottom profiler (SBP) and transient electromagnetic (TEM) data with a newly developed floating single-loop configuration. In October 2019, after the sudden drainage event, we took advantage of this unique situation and carried out complementary measurements directly on the exposed lake floor of Lakes Metzabok and Tzibaná. During this second campaign, we collected time-domain induced polarization (TDIP) and seismic refraction tomography (SRT) data. By integrating the multi-methodological data set, we (1) identify 5–6 m thick, likely undisturbed sediment sequences on the bottom of both lakes, which are suitable for future paleoenvironmental drilling campaigns, (2) develop a comprehensive geological model implying a strong interconnectivity between surface water and karst aquifer, and (3) evaluate the potential of the applied geophysical approach for the reconnaissance of the geological situation of karst lakes. This methodological evaluation reveals that under the given circumstances, (i) SBP and TDIP phase images consistently resolve the thickness of the fine-grained lacustrine sediments covering the lake floor, (ii) TEM and TDIP resistivity images consistently detect the upper limit of the limestone bedrock and the geometry of fluvial deposits of a river delta, and (iii) TDIP and SRT images suggest the existence of a layer that separates the lacustrine sediments from the limestone bedrock and consists of collapse debris mixed with lacustrine sediments. Our results show that the combination of seismic methods, which are most widely used for lake-bottom reconnaissance, with resistivity-based methods such as TEM and TDIP can significantly improve the interpretation by resolving geological units or bedrock heterogeneities, which are not visible from seismic data. Only the use of complementary methods provides sufficient information to develop comprehensive geological models of such complex karst environment

The geochemistry of carbonate diagenesis: The past, present and future

Stable carbon and oxygen isotopes (δ18O and δ13C values) and trace elements have been applied to the study of diagenesis of carbonate rocks for over 50 years. As valuable as these insights have been, many problems regarding the interpretation of geochemical signals within mature rocks remain. For example, while the δ18O values of carbonate rocks are dependent both upon the temperature and the δ18O value of the fluid, and additional information including trace element composition aids in interpreting such signals, direct evidence of either the temperature or the composition of the fluids is required. Such information can be obtained by analysing the δ18O value of any fluid inclusions or by measuring the temperature using a method such as the ‘clumped’ isotope technique. Such data speak directly to a large number of problems in interpreting the oxygen isotope record including the well‐known tendency for δ18O values of carbonate rocks to decrease with increasing age. Unlike the δ18O, δ13C values of carbonates are considered to be less influenced by diagenesis and more a reflection of primary changes in the global carbon cycle through time. However, many studies have not sufficiently emphasized the effects of diagenesis and other post‐depositional influences on the eventual carbon isotopic composition of the rock with the classic paradigm that the present is the key to the past being frequently ignored. Finally, many additional proxies are poised to contribute to the interpretation of carbonate diagenesis. Although the study of carbonate diagenesis is at an exciting point with an explosion of new proxies and methods, care should be taken to understand both old and new proxies before applying them to the ancient record