Preparative high‐performance liquid chromatography and preparative thin‐layer chromatography isolation of tocainide carbamoyl‐O‐β‐D‐glucuronide: Structural characterization by gas chromatography‐mass spectrometry and fast atom bombardment‐mass spectrometry

D.W.K. Kwok, G. Pillai, R. Vaughan, J.E. Axelson, K.M. McErlane

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Abstract

Tocainide carbamoyl‐O‐β‐D‐glucuronide, a major urinary metabolite of the antiarrhythmic drug tocainide [2‐amino‐N‐(2′, 6′‐xylyl)propanoxylidide], was isolated by preparative‐TLC and preparative‐HPLC. The isolated glucuronide was hydrolyzed in sodium hydroxide (pH > 12) to 3‐(2′, 6′‐xylyl)‐5‐methylhydantoin. This hydantoin product was also identified when tocainide was reacted with urea in urine. Structural characterization of the isolated tocainide glucuronide was carried out using GC‐MS of the permethylated derivative. The molecular ion of the permethylated glucuronide was not observed, but ion fragments at m/z 232(244), 277(288), and 334(349) were found to correspond to the postulated novel carbamoyl ester structure of the permethylated (perdeuteromethylated) glucuronide. Structural evidence for the underivatized tocainide glucuronide was obtained using fast atom bombardment‐MS. The [M+H]+ ion at m/z413 was observed. Characteristic sodium ion adducts [M+Na]+ and [M‐H+2Na]+ were also observed at m/z435 and 457, respectively. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company
Original languageUndefined/Unknown
Pages (from-to)857-861
Number of pages5
JournalJournal of Pharmaceutical Sciences
Volume79
Issue number10
DOIs
Publication statusPublished - 1990

Cite this

@article{70edb0b6d4a643a9836d8c24d2ce750a,
title = "Preparative high‐performance liquid chromatography and preparative thin‐layer chromatography isolation of tocainide carbamoyl‐O‐β‐D‐glucuronide: Structural characterization by gas chromatography‐mass spectrometry and fast atom bombardment‐mass spectrometry",
abstract = "Tocainide carbamoyl‐O‐β‐D‐glucuronide, a major urinary metabolite of the antiarrhythmic drug tocainide [2‐amino‐N‐(2′, 6′‐xylyl)propanoxylidide], was isolated by preparative‐TLC and preparative‐HPLC. The isolated glucuronide was hydrolyzed in sodium hydroxide (pH > 12) to 3‐(2′, 6′‐xylyl)‐5‐methylhydantoin. This hydantoin product was also identified when tocainide was reacted with urea in urine. Structural characterization of the isolated tocainide glucuronide was carried out using GC‐MS of the permethylated derivative. The molecular ion of the permethylated glucuronide was not observed, but ion fragments at m/z 232(244), 277(288), and 334(349) were found to correspond to the postulated novel carbamoyl ester structure of the permethylated (perdeuteromethylated) glucuronide. Structural evidence for the underivatized tocainide glucuronide was obtained using fast atom bombardment‐MS. The [M+H]+ ion at m/z413 was observed. Characteristic sodium ion adducts [M+Na]+ and [M‐H+2Na]+ were also observed at m/z435 and 457, respectively. Copyright {\circledC} 1990 Wiley‐Liss, Inc., A Wiley Company",
author = "D.W.K. Kwok and G. Pillai and R. Vaughan and J.E. Axelson and K.M. McErlane",
note = "cited By 13",
year = "1990",
doi = "10.1002/jps.2600791002",
language = "Undefined/Unknown",
volume = "79",
pages = "857--861",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
publisher = "John Wiley and Sons Inc.",
number = "10",

}

TY - JOUR

T1 - Preparative high‐performance liquid chromatography and preparative thin‐layer chromatography isolation of tocainide carbamoyl‐O‐β‐D‐glucuronide: Structural characterization by gas chromatography‐mass spectrometry and fast atom bombardment‐mass spectrometry

AU - Kwok, D.W.K.

AU - Pillai, G.

AU - Vaughan, R.

AU - Axelson, J.E.

AU - McErlane, K.M.

N1 - cited By 13

PY - 1990

Y1 - 1990

N2 - Tocainide carbamoyl‐O‐β‐D‐glucuronide, a major urinary metabolite of the antiarrhythmic drug tocainide [2‐amino‐N‐(2′, 6′‐xylyl)propanoxylidide], was isolated by preparative‐TLC and preparative‐HPLC. The isolated glucuronide was hydrolyzed in sodium hydroxide (pH > 12) to 3‐(2′, 6′‐xylyl)‐5‐methylhydantoin. This hydantoin product was also identified when tocainide was reacted with urea in urine. Structural characterization of the isolated tocainide glucuronide was carried out using GC‐MS of the permethylated derivative. The molecular ion of the permethylated glucuronide was not observed, but ion fragments at m/z 232(244), 277(288), and 334(349) were found to correspond to the postulated novel carbamoyl ester structure of the permethylated (perdeuteromethylated) glucuronide. Structural evidence for the underivatized tocainide glucuronide was obtained using fast atom bombardment‐MS. The [M+H]+ ion at m/z413 was observed. Characteristic sodium ion adducts [M+Na]+ and [M‐H+2Na]+ were also observed at m/z435 and 457, respectively. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company

AB - Tocainide carbamoyl‐O‐β‐D‐glucuronide, a major urinary metabolite of the antiarrhythmic drug tocainide [2‐amino‐N‐(2′, 6′‐xylyl)propanoxylidide], was isolated by preparative‐TLC and preparative‐HPLC. The isolated glucuronide was hydrolyzed in sodium hydroxide (pH > 12) to 3‐(2′, 6′‐xylyl)‐5‐methylhydantoin. This hydantoin product was also identified when tocainide was reacted with urea in urine. Structural characterization of the isolated tocainide glucuronide was carried out using GC‐MS of the permethylated derivative. The molecular ion of the permethylated glucuronide was not observed, but ion fragments at m/z 232(244), 277(288), and 334(349) were found to correspond to the postulated novel carbamoyl ester structure of the permethylated (perdeuteromethylated) glucuronide. Structural evidence for the underivatized tocainide glucuronide was obtained using fast atom bombardment‐MS. The [M+H]+ ion at m/z413 was observed. Characteristic sodium ion adducts [M+Na]+ and [M‐H+2Na]+ were also observed at m/z435 and 457, respectively. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company

U2 - 10.1002/jps.2600791002

DO - 10.1002/jps.2600791002

M3 - Article

VL - 79

SP - 857

EP - 861

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 10

ER -