Rapid quantification of isomeric and dehalogenated impurities in pharmaceutical raw materials using MRR spectroscopy

Neill, Justin L.; Mikhonin, Aleksandr V.; Chen, Ted; Sonstrom, Reilly E.; Pate, Brooks H.

doi:10.1016/j.jpba.2020.113474

Cited by 24 publications

(37 citation statements)

References 23 publications

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“…Overall, the introduction of both techniques has opened uncharted avenues to apply molecular rotational spectroscopy to chiral analysis. [44][45][46] Although there remains work to fully exploit the capabilities of rotational spectroscopy for quantitative chiral analysis, this mini-review illustrates the accomplishments so far and demonstrates clearly the promises of the two methods presented.…”

Section: Discussionmentioning

confidence: 81%

Assessing the performance of rotational spectroscopy in chiral analysis

et al. 2020

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Section: Discussionmentioning

confidence: 81%

Assessing the performance of rotational spectroscopy in chiral analysis

et al. 2020

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“…2 We used a set of 10 rotational transitions and the (B3LYP-D3(BJ)) predicted electric dipole moments in Table 1, quite close for both isomers. This calculation gave conformational populations of I:II=1:0.29 (7). On the assumption that the cis-/transbarrier makes the conformational population transfer negligible, a Boltzmann distribution…”

Section: Resultsmentioning

confidence: 99%

“…We illustrate the structural potential of broadband rotational spectroscopy for moderately-sized (ca. 20-40 atoms) molecules, seldom investigated in the gas phase and offering new avenues for pharmaceutical and chemical analysis 7 and quantification of crude reaction mixtures. 8 We report a first rotational study on the family of matrine alkaloids, never before examined in the gas phase.…”

Section: Introductionmentioning

confidence: 99%

Molecular Rotation Spectrum of Tetracyclic Quinolizidines: Observation of trans-Matrine and the Elusive cis-Matrine

et al. 2021

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We characterized the bis-quinolizidine tetracyclic alkaloid (5S, 6S, 7R, 11R)-matrine in a supersonic jet expansion, using chirped-pulsed broadband microwave spectroscopy. Previous crystal diffraction analyses suggested 16 diastereoisomers associated with matrine’s four carbon stereocenters but were inconclusive whether the lactamic nitrogen atom would additionally produce separated trans-/cis- diastereoisomers or if both species may interconvert through low potential barriers. Our experiment simultaneously detected trans- and cis-matrine through their rotational spectrum, confirming the possibility of conformational rearrangement in matrine alkaloids. The two matrine conformers mainly differ in the envelope or half-chair lactamic ring, as evidenced by the experimental rotational and nuclear quadrupole coupling parameters. Molecular orbital calculations with ab initio (MP2) and density functional methods (B3LYP-D3(BJ) and MN15) were tested against the experiment, additionally offering an estimation of the cis-/trans- barrier of 24.9–26.9 kJ mol–1. The experiment illustrates the structural potential of chirped-pulsed broadband microwave spectroscopy for high-resolution rotational studies of biomolecules in the range of 20–40 atoms.

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“…Moreover, very recently the technique has proved to be of fundamental use in the field of analytical chemistry as a support method for various scientific fields, for example in pharmaceutical research [27] such as in the analysis of isotopic impurities [28]. The ultimate goal in the field is to be able to create a technique that has the potential to directly analyze complex chemical mixtures and also perform chiral analyses without the need for chemical separation by chromatography [29,30]. The reader may find more insights on the on the chirped-pulse Fourier transform spectrometer in Appendix A.…”

Section: Background and Motivationmentioning

confidence: 99%

Testing the Scalability of the HS-AUTOFIT Tool in a High-Performance Computing Environment

et al. 2021

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In the last years, the development of broadband chirped-pulse Fourier transform microwave spectrometers has revolutionized the field of rotational spectroscopy. Currently, it is possible to experimentally obtain a large quantity of spectra that would be difficult to analyze manually due to two main reasons. First, recent instruments allow obtaining a considerable amount of data in very short times, and second, it is possible to analyze complex mixtures of molecules that all contribute to the density of the spectra. AUTOFIT is a spectral assignment software application that was developed in 2013 to support and facilitate the analysis. Notwithstanding the benefits AUTOFIT brings in terms of automation of the analysis of the accumulated data, it still does not guarantee a good performance in terms of execution time because it leverages the computing power of a single computing machine. To cater to this requirement, we developed a parallel version of AUTOFIT, called HS-AUTOFIT, capable of running on high-performance computing (HPC) clusters to shorten the time to explore and analyze spectral big data. In this paper, we report some tests conducted on a real HPC cluster aimed at providing a quantitative assessment of HS-AUTOFIT’s scaling capabilities in a multi-node computing context. The collected results demonstrate the benefits of the proposed approach in terms of a significant reduction in computing time.

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Rapid quantification of isomeric and dehalogenated impurities in pharmaceutical raw materials using MRR spectroscopy

Cited by 24 publications

References 23 publications

Assessing the performance of rotational spectroscopy in chiral analysis

Assessing the performance of rotational spectroscopy in chiral analysis

Molecular Rotation Spectrum of Tetracyclic Quinolizidines: Observation of trans-Matrine and the Elusive cis-Matrine

Testing the Scalability of the HS-AUTOFIT Tool in a High-Performance Computing Environment

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