Direct high-performance liquid chromatography determination of propofol and its metabolite quinol with their glucuronide conjugates and preliminary pharmacokinetics in plasma and urine of man.
Propofol (P) is metabolized in humans by oxidation to 1,4-di-isopropylquinol (Q). P and Q are in turn conjugated with glucuronic acid to the respective glucuronides, propofol glucuronide (Pgluc), quinol-1-glucuronide (Q1G) and quinol-4-glucuronide (Q4G). Propofol and quinol with their glucuronide conjugates can be measured directly by gradient high-performance liquid chromatographic analysis without enzymic hydrolysis. The glucuronide conjugates were isolated by preparative HPLC from human urine samples. The glucuronides of P and Q were present in plasma and urine, P and Q were present in plasma, but not in urine. Quinol in plasma was present in the oxidised form, the quinone. Calibration curves of the respective glucuronides were constructed by enzymic deconjugation of isolated samples containing different concentrations of the glucuronides. The limit of quantitation of P and quinone in plasma are respectively 0.119 and 0.138 microg/ml. The limit of quantitation of the glucuronides in plasma are respectively: Pgluc 0.370 microg/ml, Q1G 1.02 microg/ml and Q4G 0.278 microg/ml. The corresponding values in urine are: Pgluc 0.264 microg/ml, Q1G 0.731 microg/ml and Q4G 0.199 microg/ml. A pharmacokinetic profile of P with its metabolites is shown, and some preliminary pharmacokinetic parameters of P and Q glucuronides are given.
Institute of Anaesthesiology, Academic Hospital Sint Radboud, Nijmegen, The Netherlands. T.Vree@anes.azn.nl
T B
TB
Vree
A J
AJ
Lagerwerf
C P
CP
Bleeker
P M
PM
de Grood
D018686:Anesthetics, Intravenous / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001711:Biotransformation; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005965:Glucuronates / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D006801:Humans; D006873:Hydroquinones / Q000032:analysis* / Q000097:blood / Q000652:urine; D008171:Lung Diseases / Q000097:blood / Q000601:surgery / Q000652:urine; D008297:Male; D013058:Mass Spectrometry; D015742:Propofol / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet
D018686:Anesthetics, Intravenous; D005965:Glucuronates; D006873:Hydroquinones; D015742:Propofol