Rapid structural analysis of the in vitro and in vivo metabolism of SK & F 95448 by the combined use of thermospray liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry.
The thermospray liquid chromatography/mass spectrometry (LC/MS) interface has had a major impact on the direct analysis of the metabolic fate of xenobiotics in complex biological media. This paper outlines the rapidity and power of the LC/MS approach, and shows how detailed structural information can be obtained without recourse to individual compound isolation. This provides a great saving in time and effort. The additional specificity of liquid chromatography/tandem mass spectrometry is highlighted in identifying the sites of metabolic transformation. The ability to handle biological samples with little or no clean-up using wide high-performance liquid chromatographic gradients is a key feature of the success of this methodology.
Blake
T J
TJ
Department of Drug Metabolism and Pharmacokinetics, Smith Kline & French Research Ltd., Welwyn, Herts, UK.
Beattie
I G
IG
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D000897:Anti-Ulcer Agents / Q000032:analysis* / Q000378:metabolism; D001562:Benzimidazoles / Q000032:analysis* / Q000378:metabolism / Q000494:pharmacology; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D005243:Feces / Q000032:analysis; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology; D017506:H(+)-K(+)-Exchanging ATPase; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D011725:Pyridines / Q000032:analysis* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013056:Spectrophotometry, Ultraviolet; D005466:Fluorocarbons
D000251:Adenosine Triphosphatases; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D017506:H(+)-K(+)-Exchanging ATPase; D011725:Pyridines; C061512:SK&F 95448; D005466:Fluorocarbons