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
SN - 0022-3549
VL - 79
SP - 857
EP - 861
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
IS - 10
ER -