The Use of Deuterium Oxide as a Mobile Phase for Structural Elucidation by HPLC/UV/ESI/MS

Olsen, Mark A.; Cummings, Paul; Kennedy-Gabb, Sonya; Wagner, Brian M.; Nicol, Gordon; Munson, Burnaby

doi:10.1021/ac000316p

Cited by 58 publications

(43 citation statements)

References 31 publications

(29 reference statements)

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“…The effects of D 2 O upon chromatographic performance, specifically retention and selectivity, has been investigated for the separations of benzene, monodeutero and perdeuterobenzene, alkylbenzenes, aromatics and degradation products of amoxicillin [18,22,28]. D 2 O appeared to offer little selectivity advantages for separations of benzene from its deuterated analogs, from alkyl benzenes having aliphatic chain lengths of 1-5 and for amoxicillin degradates.…”

Section: Chromatographymentioning

confidence: 99%

“…This has been investigated by monitoring the total time required for complete exchange for probe analytes after switching from a protic to deuterated mobile phase [19,22]. Full exchange has been reported as 2.3-2.5 times the system breakthrough volume.…”

Section: Chromatographic Exchange Ratementioning

confidence: 99%

“…Subsequent investigations using popular atmospheric pressure ionization interfaces such as chemical ionization (APCI) and electrospray (ESI) showed the most facile and efficient method of H/D exchange could be accomplished dynamically oncolumn compared to post column addition of D 2 O to a protic mobile phase or flow injection of a deuterated medium into a protic carrier [20,21]. H/D exchange with either LC-MS or LC-tandem MS has been used for compound identification in forced degradation studies of the antibiotic amoxicillin [22], stability studies of an investigational substance P antagonist receptor [23] and a pharamaceutical formulation of hydralazine [20] and in drug metabolism studies to identify metabolites of denopamine, promethazine, epithilone B, an investigational ␣-amino amide, a calcium channel antagonist and a matrix metalloprotease [21,[24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

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Liquid chromatography–mass spectrometry using the hydrogen/deuterium exchange reaction as a tool for impurity identification in pharmaceutical process development

Novak

Helmy

Santos

2005

Journal of Chromatography B

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Section: Chromatographymentioning

confidence: 99%

Section: Chromatographic Exchange Ratementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Liquid chromatography–mass spectrometry using the hydrogen/deuterium exchange reaction as a tool for impurity identification in pharmaceutical process development

Novak

Helmy

Santos

2005

Journal of Chromatography B

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“…The measured mass-to-charge ratio of 309.1808 compared favorably with the calculated (expected) value of 309.1809 (accuracy ϭ Ϫ0.4 ppm; standard deviation ϭ 1.1 ppm). Replacement of the aqueous component of the HPLC eluent with D 2 O resulted in a complete exchange of all labile protons in the analyte molecule [22]. For lisinopril, the deuterium exchange experiment produced the expected mass shift of 6 Da (m/z 406,…”

Section: Positive Ion Studymentioning

confidence: 99%

Mass spectral fragmentation reactions of angiotensin-converting enzyme (ACE) inhibitors

Burinsky

Sides

2004

J. Am. Soc. Mass Spectrom.

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“…Surprisingly, this method has infrequently been applied for characterization of metabolites° [25][26][27][28][29][30][31][32][33].°The°higher°cost°of°D 2 O could be considered a certain drawback, but the consumption of D 2 O can be significantly reduced by using smaller columns and smaller solvent bottles. Alternatively, fractions can be collected and redissolved in D 2 O containing solvents.…”

Section: H/d Exchangementioning

confidence: 99%

Structural characterization of sulfadiazine metabolites using H/D exchange combined with various MS/MS experiments

Pfeifer¹,

Tuerk

Fuchs³

2005

J. Am. Soc. Mass Spectrom.

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Two major metabolites and one minor metabolite of sulfadiazine were found in pig manure, using a special combination of different MS techniques like parent and product ion scans, H/D exchange, accurate mass measurement, and MS/MS experiments with substructures. N4-acetylsulfadiazine and 4-hydroxysulfadiazine were identified as major metabolites. N4-acetylsulfadiazine could be verified by H/D exchange and comparison with product ion spectra of a synthetic reference compound. In the case of 4-hydroxysulfadiazine, the majority of possible isomers could be discounted after H/D exchange. Substructure-specific MS/MS experiments with fragment ions and comparison with product ion spectra of two references revealed the presence of 4-hydroxysulfadiazine. The minor metabolite was characterized to some degree using H/D exchange and tandem mass spectrometry in combination with a high-resolution time of flight mass spectrometer. The aminopyrimidine moiety contained an additional modification with a likely elemental composition of . Antibiotics and antimicrobial agents are used for both therapeutic and prophylactic purposes in addition to their application as growth promoters. The antimicrobial sulfonamides are one class of pharmaceuticals that is widely used. As a consequence, these compounds have been found in surface and ground water, liquid manure, and soil [3][4][5][6][7][8][9][10][11][12]. After administration to animals, the majority of the pharmaceuticals used are excreted unchanged or as phase I and phase II metabolites. As part of an environmental risk assessment, these metabolites also have to be characterized because phase I metabolites can still be active against bacteria and phase II metabolites can be converted back to the parent drug or phase I metabolites. Moreover, very little is known about the capacity of microbiological decay and the occurrence of new metabolites after incubation for several months in a manure tank.There are only a few references describing the metabolism of sulfadiazine in pigs [13,14]. After intravenous administration of 40 to 60 mg sulfadiazine per kg body weight to male pigs without coadministration of trimethoprim, only low levels of metabolites have been observed. The N-acetyl sulfadiazine was the main metabolite in plasma. Traces of 4-hydroxysulfadiazine were also detected. N-acetyl sulfadiazine and 4-hydroxysulfadiazine were the major metabolites in urine collected up to three hours after application. No further metabolites were identified and investigations in feces were not carried out.The aim of the present work was to use different mass spectrometric strategies to identify possible metabolites of the widely used drug sulfadiazine in manure originating from a pig farm. The metabolites of interest should still have a similar structure as the parent drug and, therefore, retain to a greater or lesser extent their bioactive profile against micro-organisms. Earlier investigations about the biological activity of metabolites showed action of hydroxylated metabolites of sulfadiazine ag...

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The Use of Deuterium Oxide as a Mobile Phase for Structural Elucidation by HPLC/UV/ESI/MS

Cited by 58 publications

References 31 publications

Liquid chromatography–mass spectrometry using the hydrogen/deuterium exchange reaction as a tool for impurity identification in pharmaceutical process development

Liquid chromatography–mass spectrometry using the hydrogen/deuterium exchange reaction as a tool for impurity identification in pharmaceutical process development

Mass spectral fragmentation reactions of angiotensin-converting enzyme (ACE) inhibitors

Structural characterization of sulfadiazine metabolites using H/D exchange combined with various MS/MS experiments

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