A Simple and Sensitive High-Performance Liquid Chromatographic Method for Quantification of PXD101, a Histone Deacetylase Inhibitor in Human Plasma
| Autor: | Yok Moi Khoo, Ningning Zhang, Winnie Yeo, How Sung Lee, Boon Cher Goh |
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| Rok vydání: | 2007 |
| Předmět: |
Pharmacology
Sulfonamides Chromatography Chemistry medicine.drug_class Histone deacetylase inhibitor Hydroxamic Acids Sensitivity and Specificity High-performance liquid chromatography Anticancer drug Biological fluid Histone Deacetylase Inhibitors Drug Stability Human plasma Freezing medicine Humans Pharmacology (medical) Chromatography High Pressure Liquid |
| Zdroj: | Therapeutic Drug Monitoring. 29:231-235 |
| ISSN: | 0163-4356 |
| Popis: | PXD101, a new histone deacetylase inhibitor, is currently undergoing phase I/II clinical trials as an anticancer drug. This study describes a simple and sensitive high-performance liquid chromatography ultraviolet method developed for the quantification of PXD101 in human plasma samples to support such trials. Following solid phase extraction at room temperature, the analytes were separated on a 5 mum C18 150 x 2.1 mm column using gradient elution (mobile phase of acetonitrile and 25 mM NaH2PO4, pH 2.8) at a flow rate of 0.5 mL/min and ultraviolet detection at 268 nm. Oxamflatin was used as an internal standard. PXD101 and the internal standard were eluted at about 7.9 min and 13.6 min, respectively. The lower limit of quantification of PXD101 in plasma was 10 ng/mL. The calibration curves for concentrations in the range of 10 to 2,000 ng/mL gave excellent linearity (r = 0.999). The coefficients of variation for intraday and interday assays were all less than 10%. The accuracy of all concentration determinations ranged from 98.0% to 102.0%. There were no problems with PXD101 stability following freeze-thawing, short-term exposure to room temperature, postextraction stability up to 24 hours, and sample storage at -70 degrees C for 3 months. The reported method, with dilution integrity of up to 50 fold, has the requisite sensitivity and is suitable for pharmacokinetic studies of PXD101. |
| Databáze: | OpenAIRE |
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