title: Development and validation of an ultrafiltration-UPLC-MS/MS method for rapid quantification of unbound docetaxel in human plasma.
abstract: Docetaxel lipid microsphere (DT-LM) is a novel formulation of docetaxel without Tween-80. A sensitive, robust and reproducible ultrafiltration (UF) followed by UPLC-MS/MS method was developed and validated for the quantification of unbound docetaxel in human plasma using paclitaxel as IS. Ultrafiltrate samples were chromatographed on Acquity UPLC BEH C18 column (50 mm × 2.1 mm, 1.7 μm). The mobile phase was a mixture of 10mM ammonium formate in water containing 0.2% formic acid (A) and acetonitrile containing 0.2% formic acid (B). The volume of plasma utilized was only 450 μL. The calibration curve was linear over the range of 0.2-200 ng/mL, with LLOQ of 0.2 ng/mL. The method was shown to be reliable and reproducible with intra- and inter-day precision and accuracy <±15%, and extraction recovery of 98.1-104.8%. Docetaxel was stable during stability studies, e.g., short term, post-preparation and freeze-thaw cycles. The validated method was utilized to support the pharmacological study of DT-LM in patients with advanced cancer.
authors: Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
authors: Ping
authors: P
authors: Du
authors: Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
authors: Xiaohong
authors: X
authors: Han
authors: Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
authors: Ning
authors: N
authors: Li
authors: Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
authors: Hongyu
authors: H
authors: Wang
authors: Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
authors: Sheng
authors: S
authors: Yang
authors: Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
authors: Yuanyuan
authors: Y
authors: Song
authors: Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China. Electronic address: syuankai@cicams.ac.cn.
authors: Yuankai
authors: Y
authors: Shi
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D000077143:Docetaxel; D004355:Drug Stability; D006801:Humans; D016014:Linear Models; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D043823:Taxoids / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D014462:Ultrafiltration / Q000379:methods*
chemical_list: D043823:Taxoids; D000077143:Docetaxel
keywords: Docetaxel lipid microsphere; Human plasma; UPLC-MS/MS; Ultrafiltration; Unbound analyte