Evaluation of the use of UPLC-TOFMS with simultaneous [14C]-radioflow detection for drug metabolite profiling: application to propranolol metabolites in rat urine.
The non-selective beta-adrenergic receptor antagonist propranolol [1-(isopropylamino)-3-(1-naphthoxy)-2-propanol] is metabolised extensively in vivo. Enumerating and identifying the many metabolites that result from multiple biotransformations provides a considerable analytical challenge, greatly aided by efficient chromatography coupled to sensitive mass spectrometric detection. Here the use of the newly introduced high-resolution technique of "ultra performance liquid chromatography" (UPLC) linked to quadrupole time-of-flight mass spectrometry (TOFMS) with simultaneous [(14)C]-radioflow detection was applied to rapid metabolite profiling. [14C]-propranolol, dosed intraperitoneally to rat at 25 mg kg(-1) and 200 microCi kg(-1) was used as a model compound for this evaluation. Some 14 metabolites were detected in the urine by this technique including a number of conjugated metabolites such as sulphates, several isobaric glucuronides and two novel di-glucuronides.
Department of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics (SORA), Faculty of Medicine, Imperial College London, South Kensington, London SW7 2AZ, UK.
T J
TJ
Athersuch
R L
RL
Sison
A S J
AS
Kenyon
J A
JA
Clarkson-Jones
I D
ID
Wilson
D000319:Adrenergic beta-Antagonists / Q000032:analysis / Q000493:pharmacokinetics* / Q000652:urine*; D000818:Animals; D001711:Biotransformation; D002250:Carbon Radioisotopes / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D011433:Propranolol / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine*; D051381:Rats; D017208:Rats, Wistar; D016482:Urinalysis / Q000379:methods
D000319:Adrenergic beta-Antagonists; D002250:Carbon Radioisotopes; D011433:Propranolol