Separatory determination of diastereomeric ibuprofen glucuronides in human urine by liquid chromatography/electrospray ionization-mass spectrometry.
A method for the separatory determination of diastereomeric isomers of glucuronic acid conjugates of ibuprofen having a carboxyl group at the chiral center by liquid chromatography (LC)/electrospray ionization (ESI)-mass spectrometry (MS) has been developed. The authentic specimens of acyl glucuronides of R(-)- and S(+)-ibuprofen were chemically synthesized by the Mitsunobu reaction. In the ESI mode, the glucuronides were characterized by an abundant quasi-molecular ion [M-H]-, and the formation of the negative ion was markedly influenced by a drift voltage. The resolution of diastereomeric isomers was achieved on a Develosil ODS-HG-5 column with 20 mM ammonium acetate (pH 5.0):acetonitrile (5:2, v/v) as a mobile phase where diastereomers were monitored with a corresponding quasi-molecular ion. After oral administration of racemic ibuprofen, a preferential excretion of (S)-ibuprofen glucuronide into the urine was observed.
Ikegawa
S
S
Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Murao
N
N
Oohashi
J
J
Goto
J
J
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification / Q000652:urine*; D002853:Chromatography, Liquid / Q000379:methods*; D005965:Glucuronates / Q000737:chemistry / Q000302:isolation & purification / Q000652:urine*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000737:chemistry / Q000302:isolation & purification / Q000652:urine*; D013058:Mass Spectrometry / Q000379:methods*; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005965:Glucuronates; D007052:Ibuprofen