RESUMO
RATIONALE: Dispersity values are considered critical quality attributes for the quality control of poly(ethylene glycol) formulations due to the direct impact on drug performance. However, when these polymers are analysed using mass spectrometry, the design of the mass analyser can impact the oligomer response and affect the obtained dispersity values, so further understanding is needed. METHODS: The deconvoluted electrospray ionisation mass spectra of poly(ethylene glycol)s obtained using supercritical fluid chromatography (SFC) hyphenated to different mass analysers were compared, and visualisation diagrams were used to understand the differences in the dispersity value calculations. Five calibration approaches based on a surrogate single oligomer that represents the whole distribution, or the whole distribution itself, for response selection, were used to evaluate ionisation efficiency prior to quantitation. The impact of using an internal standard (ISTD) on the expanded uncertainty was also assessed. RESULTS: Although there were challenges related to the resolution of multiply charged species when low-resolution instruments were used, similar quantitation capabilities were obtained to those when high-resolution mass analysers were used. Evaluation of approaches using a surrogate oligomer or the whole distribution suggested the independence of both approaches and a constant ionisation efficiency across the oligomer chain length. The higher degree of chromatographic resolution of SFC allowed incorporating a monodispersed ISTD to improve the accuracy and precision of the method. CONCLUSIONS: The use of low resolution mass analysers was sufficient to provide accurate and precise dispersity values; however, higher resolution instruments were recommended for characterisation due to the improved mass resolution of ions. The introduction of a monodispersed ISTD improved precision without compromising the calculated dispersity value due to the lack of analyte suppression.
RESUMO
Poly(ethylene glycols) are complex polymers often added to pharmaceutical formulations to improve drug solubility and delivery. One of the main challenges when using chromatographic techniques coupled to mass spectrometry is the unselective ionization of poly(ethylene glycols) oligomers. Additionally, when the chain length is large enough, multiple charged species are formed, further complicating the mass spectra and processing. This study uses the advanced oligomer separation provided by supercritical fluid chromatography with a mass spectrometry approach that selectively ionizes poly(ethylene glycols) as ammoniated molecules to simplify data analysis and facilitate batch-to-batch comparisons. Several visual representations of the response of the ionization events based on the polymer molecular weight and the repeating unit were used to elucidate trends in ionization. Evaluation of the influence of the oligomer length and end-group on the electrospray ionization of the polymer allowed the development of a process to enable selective ionization for these complex polymers.
RESUMO
An ultrahigh-performance supercritical fluid chromatography-mass spectrometry (UHPSFC-MS) method has been developed as a rapid and reliable analytical method for the detection and quantification of elemental sulfur in mineral transformer oil. The method described in this paper is based on the selective reaction of elemental sulfur with triphenylphosphine (TPP). The derivatisation of elemental sulfur requires minimal sample preparation and resulted in the formation of a single compound, namely triphenylphosphine sulfide (TPPS). This derivative is quantified from the complex oil composition using electrospray ionisation-mass spectrometry (ESI-MS) in selected ion monitoring (SIM) mode, and the reported UHPSFC-MS method allows detection and quantification of the derivative at ppb levels. As sulfur contamination in mineral transformer oil has been linked to costly failures of oil/paper-based power transformers due to corrosion, the analytical approach is demonstrated through its application to mineral oil samples from in service and decommisioned power transformers. The method is ideal as a routine test or to confirm the presence of elemental sulfur in samples where corrosion has occurred.
RESUMO
Diastereoisomeric mixtures of cis-uvariamicin I (15R,16R,19S,20S,36S and 15S,16S,19R,20R,36S) and cis-reticulatacin (17R,18R,21S,22S,36S and 17S,18S,21R,22R,36S) were synthesized to determine the stereochemistry of the natural products isolated from Annona muricata. It was not possible to resolve a mixture of the four synthetic isomers using chiral HPLC, but the mixed isomers could be distinguished using chiral HPLC EIMS with extracted fragment ion analysis. Comparison of synthetic standards with the natural isolate revealed that cis-uvariamicin I and cis-reticulatacin are present in nature as mixtures of threo-cis-threo diastereoisomers. It is suggested that the nomenclature for the natural products is amended as follows: (15R,16R,19S,20S,36S)-cis-uvariamicin I (cis-uvariamicin IA); (15S,16S,19R,20R,36S)-cis-uvariamicin I (cis-uvariamicin IB); (17R,18R,21S,22S,36S)-cis-reticulatacin (cis-reticulatacin A); (17S,18S,21R,22R,36S)-cis-reticulatacin (cis-reticulatacin B).