Simultaneous analysis of quaternary ammonium cations and corresponding halide counterions by pyrolysis gas chromatography / mass spectrometry.

The use of quaternary ammonium compounds (QACs) as disinfectants has increased tremendously in the COVID-10 pandemic to inactivate Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV2). Dialkyldimethylammonium halides represent a frequently used type among QACs. Different halide anions, each ionically linked to the same quaternary ammonium cation, show clear differences in biocidal activity, toxicity and allergic potential. Likewise, the alkyl chain length at the ammonium cation induces different biocidal efficacy and toxicology. Therefore, the object of this research was to develop a rapid and reliable method for the detection of ammonium cation and halide anion in a single analytical run. For that purpose, a gas chromatography mass spectrometry (GC/MS) method was developed for QACs of the dialkyldimethylammonium type. Pyrolytic conversion of the QACs in the injector port of the gas chromatograph into volatile molecule species allows fast and reliable subsequent GC/MS analysis. The developed method is suited for the determination of both the quaternary ammonium cation and the corresponding halide anion in a single gas chromatographic run. The application of this method to bulk material and standard material of explicitly specified didecyldimethylammonium chloride revealed deviations from the manufacturer's specifications in a range up to four-fifths. Furthermore, didecyldimethylammonium chloride was detected in a disinfectant that does not comply with the labeling requirement for biocidal ingredients. With the method presented, results can be obtained for disinfectants with minimum effort within seven minutes.

Discrepancies in the German Pharmacopoeia procedure for quality control of Quillaja saponin extracts.

This study focused on the evaluation of Quillaja saponin extracts with the additional quality designation DAB-which means the abbreviation of the German Pharmacopoeia (Deutsches Arzneibuch). This label suggests that Quillaja saponin extracts marked in this way are of pharmacopoeial quality and thus stand out from other Quillaja saponin extracts. The DAB ninth edition listed Quillaia saponin as a reagent. According to DAB, its quality must be checked by thin-layer chromatography (TLC), and three closely spaced zones in a defined retention factor (Rf) interval specify the saponin reagent. All the Quillaja saponin extracts obtained from different manufacturers and labeled as DAB quality complied with the TLC test. However, the analysis with high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (HPLC-Q-ToF-MS) clearly showed additionally an intense peak pattern of Madhuca saponins in all measured samples. The TLC test for Mahua seed cake, which is the press residue from Madhuca longifolia, surprisingly showed the same three closely spaced zones in the defined Rf interval. The three zones could be identified as Mi-saponins from Madhuca after scraping and extracting them from the stationary phase of the TLC plate and subsequent measurement by HPLC-Q-ToF-MS. Therefore, the specification of the saponin reagent in DAB characterizes erroneously Madhuca saponins that are not listed as a saponin plant source for the saponin reagent.

Collision cross sections obtained with ion mobility mass spectrometry as new descriptor to predict blood-brain barrier permeation by drugs.

Evaluating the ability of a drug to permeate the blood-brain barrier is not a trivial task due to the structural complexity of the central nervous system. Nevertheless, it is of immense importance to identify related properties of the drugs either to be able to produce a desired effect in the brain or to avoid unwanted side effects there. In the past, multiple methods have been used for that purpose. However, these are sometimes methodologically problematic and do not claim universal validity. Therefore, additional new methods for judging blood-brain barrier penetration by drugs are advantageous. Accordingly, within the scope of this study, we tried to introduce a new structure-derived parameter to predict the blood-brain barrier permeation of small molecules based on ion mobility mass spectrometry experiments - the collision cross section, as an illustration of the branching and the molecular volume of a molecule. In detail, we used ion mobility quadrupole time-of-flight mass spectrometric data of 46 pharmacologically active small-molecules as well as literature-derived permeability and lipophilicity data to set up our model. For the first time we were able to show a strong correlation between the brain penetration of pharmacologically active ingredients and their mass spectrometric collision cross sections.

Identification of thymol phase I metabolites in human urine by headspace sorptive extraction combined with thermal desorption and gas chromatography mass spectrometry.

Development of a novel highly sensitive headspace sorptive extraction (HSSE) method in combination with thermal desorption gas chromatography coupled to a mass spectrometer (TD-GC/MS) allowed the identification of thymol and several phase I metabolites in human urine. Combined with an enzymatic hydrolysis of glucuronated or sulphated phase II metabolites of thymol and of the respective phase I metabolites prior to analysis, even trace quantities of hitherto not detected thymol phase I metabolites could be identified in urine samples of test persons after oral administration of 50mg thymol. It was proven, that human metabolism leads to a hydroxylation of the aromatic ring as well as of the iso-propyl side chain. Hydroxylation of the iso-propyl group results in the formation of the rather unstable p-cymene-3,8-diol and the corresponding dehydration product p-cymene-3-ol-8-ene which could be clearly detected in human urine samples. Furthermore, the aromatic hydroxylation products p-cymene-2,5-diol, its oxidation product p-cymene-2,5-dione and p-cymene-2,3-diol were also unambiguously identified by comparison with synthesized reference compounds.