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Titolo:
AUTOMATED-DETERMINATION OF DEXTROMETHORPHAN AND ITS MAIN METABOLITES IN HUMAN PLASMA BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AND COLUMN-SWITCHING
Autore:
HARTTER S; BAIER D; DINGEMANSE J; ZIEGLER G; HIEMKE C;
Indirizzi:
UNIV MAINZ,DEPT PSYCHIAT,UNTERE ZAHLBACHER STR 8 D-55101 MAINZ GERMANY UNIV MAINZ,DEPT PSYCHIAT D-55101 MAINZ GERMANY F HOFFMANN LA ROCHE & CO LTD GRENZACH WYHLEN GERMANY F HOFFMANN LA ROCHE & CO LTD,DEPT CLIN PHARMACOL CH-4002 BASEL SWITZERLAND INST PSYCHOSOMAT RES STUTTGART GERMANY
Titolo Testata:
Therapeutic drug monitoring
fascicolo: 3, volume: 18, anno: 1996,
pagine: 297 - 303
SICI:
0163-4356(1996)18:3<297:AODAIM>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
3 METABOLITES; PHENOTYPE; URINE; POLYMORPHISM; MEPHENYTOIN; GENOTYPE;
Keywords:
DEXTROMETHORPHAN; DEXTRORPHAN; HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY; COLUMN SWITCHING; PHARMACOGENETICS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
24
Recensione:
Indirizzi per estratti:
Citazione:
S. Hartter et al., "AUTOMATED-DETERMINATION OF DEXTROMETHORPHAN AND ITS MAIN METABOLITES IN HUMAN PLASMA BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AND COLUMN-SWITCHING", Therapeutic drug monitoring, 18(3), 1996, pp. 297-303

Abstract

An automated column-switching technique coupled to isocratic high-performance liquid chromatography (HPLC) with fluorescence detection was developed for simultaneous determination of dextromethorphan and its three major metabolites, dextrorphan, hydroxymorphinan, and methoxymorphinan. After cleavage of conjugates by incubation with glucuronidase-arylsulfatase at 37 degrees C for 15 h, plasma samples were injected directly into the HPLC system. Dextromethorphan and metabolites were retained on a cleanup column (10 x 4.6 mm internal diameter [ID]) filled with cyanopropyl (CN) material (Hypersil CPS, 10-mu m particle size) while interfering proteins and lipids were washed to waste. After column switching, the drugs were eluted from the cleanup column and separated on Spherisorb CN material (5-mu m particle size, column size 250 x 4.6 mm ID). Fluorescence detection was carried out with an excitation wavelength of 220 nm and an emission wavelength of 305 nm. Sample cleanup and HPLC separation were completed within 20 min. Regression analyses found linearity (r > 0.99) between drug concentration and detectorresponse over a wide range-5-220 ng/ml for dextromethorphan, 5-550 ng/ml for dextrorphan, 5-500 ng/ml for hydroxymorphinan, and 5-200 ng/mlfor methoxymorphinan. The limit of quantification was similar to 5 ng/ml, and the recovery was >90% for all compounds. At concentrations of20-500 ng/ml, the intra- and interassay coefficients of variation ranged from 3.5 to 14.6% and from 7.0 to 14.0%, respectively. The method is suitable for in vivo phenotyping of CYP2D6 activity, which catalyzes the O-demethylation of dextromethorphan to dextrorphan, and is also applicable to pharmacokinetic studies in man.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 12:39:57