Validated LC-MS/MS methods for the determination of risperidone and the enantiomers of 9-hydroxyrisperidone in human plasma and urine.
Two liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) methods are described, one for the quantitative determination of risperidone and the enantiomers of its active metabolite 9-hydroxyrisperidone (paliperidone) in human plasma and the other for the determination of the enantiomers of 9-hydroxyrisperidone in human urine. The plasma method is based on solid-phase extraction of 200 microl of sample on a mixed-mode sorbent, followed by separation on a cellulose-based LC column with a 13.5-min mobile phase gradient of hexane, isopropanol and ethanol. After post-column addition of 10 mM ammonium acetate in ethanol/water, detection takes place by ion-spray tandem mass spectrometry in the positive ion mode. Method validation results show that the method is sufficiently selective towards the enantiomers of 7-hydroxyrisperidone and capable of quantifying the analytes with good precision and accuracy in the concentration range of 0.2-100 ng/ml. An accelerated (run time of 4.3 min) and equally valid method for the enantiomers of 9-hydroxyrisperidone alone in plasma is obtained by increasing the mobile phase flow-rate from 1.0 to 2.0 ml/min and slightly adapting the gradient conditions. The urine method is based on the same solid-phase extraction and chromatographic approach as the accelerated plasma method. Using 100 microl of sample, (+)- and (-)-9-hydroxyrisperidone can be quantified in the concentration range 1-2000 ng/ml. The accelerated method for plasma and the method for urine can be used only when paliperidone is administered instead of risperidone, as there is insufficient separation of the 9-hydroxy enantiomers from the 7-hydroxy enantiomers, the latter ones being present only after risperidone administration.
Department of Bioanalysis, Johnson & Johnson Pharmaceutical Research and Development, a Division of Janssen Pharmaceutica N.V., Turnhoutseweg 30, B-2340 Beerse, Belgium. MDMEULDE@PRDBE.jnj.com
Marc
M
De Meulder
Bart M M
BM
Remmerie
Ronald
R
de Vries
Luc L A
LL
Sips
Sandra
S
Boom
Edwin W J
EW
Hooijschuur
Nico C
NC
van de Merbel
Philip M M B L
PM
Timmerman
D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D007555:Isoxazoles / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics / Q000652:urine; D000068882:Paliperidone Palmitate; D011743:Pyrimidines / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics / Q000652:urine; D018967:Risperidone / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics / Q000652:urine; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
D007555:Isoxazoles; D011743:Pyrimidines; D018967:Risperidone; D000068882:Paliperidone Palmitate