Quantitative determination of DRF-1042 in human plasma by HPLC: validation and application in clinical pharmacokinetics
| العنوان: | Quantitative determination of DRF-1042 in human plasma by HPLC: validation and application in clinical pharmacokinetics |
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| المؤلفون: | Rao N. V. S. Mamidi, Kasiram Katneni, Vijay V. Upreti, Nuggehally R. Srinivas |
| المصدر: | Biomedical Chromatography. 17:385-390 |
| بيانات النشر: | Wiley, 2003. |
| سنة النشر: | 2003 |
| مصطلحات موضوعية: | Serial dilution, Calibration curve, Clinical Biochemistry, Analytical chemistry, Antineoplastic Agents, Sensitivity and Specificity, Biochemistry, High-performance liquid chromatography, Analytical Chemistry, Pharmacokinetics, Neoplasms, Drug Discovery, Humans, Sample preparation, Molecular Biology, Chromatography, High Pressure Liquid, Pharmacology, Chromatography, Elution, Chemistry, Reproducibility of Results, General Medicine, Standard curve, Human plasma, Calibration, Camptothecin |
| الوصف: | A simple and sensitive high-performance liquid chromatography (HPLC) method has been developed and validated for the determination of DRF-1042, a novel orally active camptothecin (CPT) analog, in human plasma. The sample preparation was a simple deproteinization with acidified methanol yielding almost 100% recovery of DRF-1042. An isocratic reverse-phase HPLC separation was developed on a Supelcosil-LC318 column (250 × 4.6 mm, 5 µm) with mobile phase consisting of 1% v/v triethylamine acetate, pH 5.5 and acetonitrile (80:20, v/v) at a flow rate of 1.0 mL/min. The eluate was monitored with a fluorescence detector set at excitation and emission wavelengths of 370 and 430 nm, respectively. The standard curves were linear (r2 > 0.999) in the concentration ranges 5.0–2004 ng/mL. The lower limit of quantification (LLQ) of the assay was 5 ng/mL. The mean measured quality control (QC) concentrations (range 5 ng/mL to 40 µg/mL) deviated from the nominal concentrations in the range of −10.5–0.08 and −14.5–7.97%, inter- and intra-day, respectively. The inter- and intra-day precisions in the measurement of QC samples at four tested concentrations, were in the range 0.64–5.89% relative standard deviation (RSD) and 0.33–14.7% RSD, respectively. The method was found to be suitable for measurement of plasma concentrations above the calibration curve after serial dilutions. Stability of DRF-1042 was confirmed in a battery of studies, viz., on bench-top, in the auto-sampler, in the stock solutions, after four quick freeze–thaw cycles, up to one month at −20C in human plasma and up to 2 months in the ex vivo samples. The method is simple, sensitive and reliable and has been successfully implemented to investigate the clinical pharmacokinetics of DRF-1042 in cancer patients in a phase I clinical trial. Copyright © 2003 John Wiley & Sons, Ltd. |
| تدمد: | 1099-0801 0269-3879 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2fcf029a96fa1d8f675ccf1c14390f4b https://doi.org/10.1002/bmc.253 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....2fcf029a96fa1d8f675ccf1c14390f4b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10990801 02693879 |
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