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Titolo:
Adaptation of solid phase extraction to an automated column switching method for online sample cleanup as the basis of a facile and sensitive high-performance liquid chromatographic assay for paclitaxel in human plasma
Autore:
Supko, JG; Nair, RV; Seiden, MV; Lu, H;
Indirizzi:
Massachusetts Gen Hosp, Div Hematol Oncol, Clin Pharmacol Lab, Boston, MA 02114 USA Massachusetts Gen Hosp Boston MA USA 02114 acol Lab, Boston, MA 02114 USA Harvard Univ, Sch Med, Boston, MA 02114 USA Harvard Univ Boston MA USA 02114 vard Univ, Sch Med, Boston, MA 02114 USA
Titolo Testata:
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
fascicolo: 5, volume: 21, anno: 1999,
pagine: 1025 - 1036
SICI:
0731-7085(199912)21:5<1025:AOSPET>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
METASTATIC BREAST-CANCER; LUNG-CANCER; CLINICAL PHARMACOKINETICS; ULTRAVIOLET DETECTION; BIOLOGICAL-FLUIDS; 96-HOUR INFUSION; OVARIAN-CANCER; MOUSE PLASMA; CELL-LINES; I TRIAL;
Keywords:
paclitaxel; high-performance liquid chromatography; column switching; analysis; plasma; pharmacokinetics; human, anticancer agents;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Supko, JG Massachusetts Gen Hosp, Div Hematol Oncol, Clin Pharmacol Lab, 55 Fruit St,GRJ1025, Boston, MA 02114 USA Massachusetts Gen Hosp 55 Fruit St,GRJ1025 Boston MA USA 02114 A
Citazione:
J.G. Supko et al., "Adaptation of solid phase extraction to an automated column switching method for online sample cleanup as the basis of a facile and sensitive high-performance liquid chromatographic assay for paclitaxel in human plasma", J PHARM B, 21(5), 1999, pp. 1025-1036

Abstract

An improved method for assaying paclitaxel in human plasma by high-performance liquid chromatography (HPLC) with UV detection at 227 nm has been developed by adapting previously reported sample preparation methods and chromatographic conditions to facilitate semi-automated sample cleanup using a column switching technique. Manual sample manipulations were limited to isolating the drug and internal standard from plasma (1.0 mi) by liquid-liquid extraction using tert-butyl methyl ether. The sample extract was initially loaded onto a short cartridge column containing a cyanopropyl stationary phase. During the predetermined time interval that the drug and internal standard eluted from the cartridge, 1.50-2.20 min, a fully automated 6-position switching valve was used to direct the effluent onto an octylsilica analytical column. The same mobile phase, composed of acetonitrile-methanol- ammonium acetate buffer (pH 5.0;20 mM) (76:19:105, v/v/v) and delivered at flow rate of 1.0 ml/min, was used for both separations. The overall retention times of paclitaxel and the internal standard were 10.9 and 18.1 min, respectively. The analytical method was thoroughly validated for quantitating paclitaxel in plasma at concentrations ranging from 6 to 586 nM (5-500 ng/ml). The lowest concentration of paclitaxel measured with acceptable day-to-day accuracy (100.2%) and precision (RSD 11.7%, n = 21, 5 months) was 6 nM (5 ng/ml). The sensitivity and selectivity of the assay proved to be more than adequate for monitoring steady-state plasma concentrations of the drug whenadministered to cancer patients as a 96 h continuous intravenous infusion in combination with other anticancer agents, such as doxorubicin and topotecan. Moreover, the heart-cutting procedure prevented the problematic introduction of interfering nonpolar plasma components onto the analytical column, thereby enhancing sample throughput while decreasing the technical demands of the assay. The method was found to be extremely reproducible and robust during extended use for the routine analysis of plasma specimens acquiredfrom several clinical trials. (C) 1999 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 06:24:32