Development and Validation of an HPLC-UV Method for Sorafenib Quantification in Human Plasma and Application to Patients With Cancer in Routine Clinical Practice
| Autor: | Vanesa Escudero-Ortiz, Juan José Pérez-Ruixo, Belén Valenzuela |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Niacinamide
Sorafenib Drug Metabolic Clearance Rate media_common.quotation_subject Antineoplastic Agents Pharmacology Lapatinib Therapeutic index Neoplasms medicine Humans Pharmacology (medical) Chromatography High Pressure Liquid media_common Dose-Response Relationship Drug medicine.diagnostic_test business.industry Phenylurea Compounds Reproducibility of Results Cancer medicine.disease Human plasma Therapeutic drug monitoring Area Under Curve Calibration Toxicity Quinazolines Spectrophotometry Ultraviolet Drug Monitoring business medicine.drug |
| Zdroj: | Therapeutic Drug Monitoring. 36:317-325 |
| ISSN: | 0163-4356 |
| DOI: | 10.1097/ftd.0000000000000027 |
| Popis: | Several factors such as low therapeutic index, large interindividual variability in systemic exposure, and the relationships between exposure and toxicity for sorafenib could justify its therapeutic drug monitoring (TDM). To support TDM, a selective and precise high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method was developed and validated for the determination of sorafenib in human plasma.After protein precipitation with acetonitrile, sorafenib and lapatinib (internal standard) were separated using isocratic elution on a Kromasil C18 column using a mobile phase of acetonitrile and 20 mmol/L ammonium acetate in a proportion 53:47 (vol/vol) pumped at a constant flow rate of 1.2 mL/min. Quantification was performed at 260 nm. Validation experiments were carried out after the guidelines for Bioanalytical Method Validation published by the Food and Drug Administration and the European Medicines Agency.Calibration curves were linear over the range 0.1-20 mcg/mL. Inter- and intra-day coefficients of variation were3%. The limit of detection and the lower limit of quantification were 0.06 and 0.1 mcg/mL, respectively. Recoveries of sorafenib from plasma were99% in all cases.This method was successfully applied to the determination of the drug in the plasma of 2 patients with cancer receiving sorafenib 200 and 400 mg orally twice daily, respectively, and could be useful for TDM of sorafenib in routine clinical practice. |
| Databáze: | OpenAIRE |
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