On-line H/D exchange LC–MS strategy for structural elucidation of pharmaceutical impurities

Liu, David Q.; Wu, Lei; Sun, Meng; MacGregor, Paul

doi:10.1016/j.jpba.2007.01.019

Cited by 50 publications

(33 citation statements)

References 23 publications

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“…3. Similar isotope exchange techniques have been used in past metabolomics experiments (Liu et al 2001(Liu et al , 2007Lam and Ramanathan 2002). To lessen the amount of labeled D 2 O needed, these prior experiments often introduced D 2 O in the gas phase at the ion source, which results in less complete D/H exchange than the method used in the current study (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Heuristic rules based on stoichiometric restrictions and/or natural isotopologue Fiehn 2006, 2007) abundances can help, as can stable isotope labeling (Baran et al 2010), most frequently done with nitrogen ( 15 N) or carbon ( 13 C). Here we apply a technique based on post-extraction deuterium (D) labeling of metabolites (Liu et al 2001(Liu et al , 2007 to the elucidate abundant metabolic features detected in a model mixedspecies microbial community.…”

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Deuterium-exchange metabolomics identifies N-methyl lyso phosphatidylethanolamines as abundant lipids in acidophilic mixed microbial communities

et al. 2011

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Natural microbial communities are extremely diverse and contain uncharacterized but functionally important small molecules. By coupling a deuterium (D) labeling technique to high mass accuracy untargeted liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) metabolomic analysis, we found that natural acidophilic microbial biofilms dominated by bacteria of the genus Leptospirillum contained unusual lyso phosphatidylethanolamine (PE) lipids in high abundance (more than 10 nmol/mg of dry biomass). The unusual polar head group structure of these lipids is similar to lipids found in phylogenetically unrelated acidophilic chemoautolithotrophs and may be related to the affinity of these lipids for iron and calcium ions. Correlations of lyso phospholipid and proteome abundance patterns suggest a link between the lyso phospholipids and the UBA-type substrain of Leptospirillum group II. By combining untargeted metabolomics with D exchange we demonstrate the ability to identify cryptic but biologically functional small molecules in mixed microbial communities.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Deuterium-exchange metabolomics identifies N-methyl lyso phosphatidylethanolamines as abundant lipids in acidophilic mixed microbial communities

et al. 2011

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“…5 shows a typical case where HDE values evidently afforded good support to predicted structures of two hydrolytic products of rosuvastatin [unpublished data]. The utility of LC-MS HDE as a tool for IMP identification in pharmaceutical process development has been exemplified by Liu et al [106]. Also, HDE was utilized for the exploration of mass fragmentation mechanism by Debrauwer et al [107].…”

Section: Lc-ms and Variantsmentioning

confidence: 99%

“…(iv) Recording of H/D exchange (HDE) spectrum at optimized MS parameters: The HDE experiments are usually performed by using D 2 O in the mobile phase, which is a simplest and most accurate strategy for on-line HDE. Some alternate strategies for on-line HDE of targeted analytes have also been proposed by Liu et al [106]. One of these requires infusion of D 2 O through a separate channel when the peak of interest starts eluting.…”

Section: Sample Preparationmentioning

confidence: 99%

A critical review on the use of modern sophisticated hyphenated tools in the characterization of impurities and degradation products

Singh

Handa

Narayanam

et al. 2012

Journal of Pharmaceutical and Biomedical Analysis

188

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“…The HPLC gradient was ramped from 25% B to 75% B linearly in 4 min. When performing the hydrogen/ deuterium (H/D) exchange experiments, 0.1% FA in deuterated water (D 2 O) was used replacing mobile phase A [28]. The mobile phase flow rate was set at 1 mL/min, of which 250 L/min was split into the API source of a mass spectrometer by an Acurate splitter (LC Packings, Sunnyvale, CA, USA).…”

Section: Hplc Separation Conditionsmentioning

confidence: 99%

Gas-phase Meerwein reaction of epoxides with protonated acetonitrile generated by atmospheric pressure ionizations

Liu

Kord

2010

J. Am. Soc. Mass Spectrom.

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Ethylnitrilium ion can be generated by protonation of acetonitrile (when used as the LC-MS mobile phase) under the conditions of atmospheric pressure ionizations, including electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) as well as atmospheric pressure photoionization (APPI). Ethylnitrilium ion (CH 3 Ϫ C ϵ N ϩ H and its canonical form CH 3 Ϫ C ϩ ϭ NH) is shown to efficiently undergo the gas-phase Meerwein reaction with epoxides. This reaction proceeds by the initial formation of an oxonium ion followed by three-to-five-membered ring expansion via an intramolecular nucleophilic attack to yield the Meerwein reaction products. The density functional theory (DFT) calculations at the B3LYP/6-311ϩG(d,p) level show that the gas-phase Meerwein reaction is thermodynamically favorable. Collision-induced dissociation (CID) of the Meerwein reaction products yields the net oxygen-by-nitrogen replacement of epoxides with a characteristic mass shift of 1 Da, providing evidence for the cyclic nature of the gas-phase Meerwein reaction products. The gas-phase Meerwein reaction offers a novel and fast LC-MS approach for the direct analysis of epoxides that might be of genotoxic concern during drug development. Understanding and utilizing this unique gas-phase ion/molecule reaction, the sensitivity and selectivity for quantitation of epoxides can be enhanced. (J Am Soc Mass Spectrom 2010, 21, 1802-1813) © 2010 American Society for Mass Spectrometry G as-phase ion/molecule reactions are fast, efficient, and highly sensitive to the fine structural variations such as relative positions of functional groups. Their product distributions often provide diagnostic information for structural characterization of both reactant ions and neutral molecules [1][2][3][4]. Ion/ molecule reactions have also contributed significantly to the elucidation of organic reaction mechanisms, helping to bridge the gap between gas-phase ion chemistry and condensed-phase organic chemistry. It also provides access to key properties and intrinsic reactivities of a great variety of solvent-and counterion-free gaseous ions and, as such, constitutes a powerful tool for chemical studies. Many classic organic reactions have been studied in the gas phase using the mass spectrometric methods [5][6][7][8][9][10][11][12][13][14]. Recently, with the advent of electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI), mass spectrometry has been widely used as an analytical tool for the study of atmospheric pressure ion/molecule reactions. These gas-phase reactions can even yield detailed information regarding the individual reaction step of the catalytic cycles, and thus allow the study of transient intermediates that have not been accessible previously by the condensed-phase techniques [15,16].Epoxides are common reagents or key intermediates in a wide variety of synthetically important condensedphase reactions, including asymmetric synthesis via the opening of the oxirane ring [17][18][19]. For example, Meerwein fi...

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On-line H/D exchange LC–MS strategy for structural elucidation of pharmaceutical impurities

Cited by 50 publications

References 23 publications

Deuterium-exchange metabolomics identifies N-methyl lyso phosphatidylethanolamines as abundant lipids in acidophilic mixed microbial communities

Deuterium-exchange metabolomics identifies N-methyl lyso phosphatidylethanolamines as abundant lipids in acidophilic mixed microbial communities

A critical review on the use of modern sophisticated hyphenated tools in the characterization of impurities and degradation products

Gas-phase Meerwein reaction of epoxides with protonated acetonitrile generated by atmospheric pressure ionizations

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