title: Simultaneous determination of bendamustine and its active metabolite, gamma-hydroxy-bendamustine in human plasma and urine using HPLC-fluorescence detector: application to a pharmacokinetic study in Chinese cancer patients.
abstract: A simple, sensitive and cost-effective assay based on reversed phase high performance liquid chromatography (RP-HPLC) with isocratic mode for simultaneous determination of bendamustine (BM) and its active metabolite, gamma-hydroxy-bendamustine (γ-OH-BM) in human plasma and urine was developed and validated. Sample preparation involved protein precipitation by 10% perchloric acid-methanol solution. The peaks were recorded by using fluorescence detector (excitation wavelength 328 nm and emission wavelength 420 nm). The calibration curves were linear over concentration ranges of 8.192-10,000 ng mL(-1) and 5-1,000 ng mL(-1) for BM in human plasma and urine as well as 10-1,000 ng mL(-1) and 5-1,000 ng mL(-1) for γ-OH-BM in human plasma and urine, respectively. Intra- and inter-run precisions of BM and γ-OH-BM were less than 15% and the bias were within ± 15% for both plasma and urine. This validated method was successfully applied to a pharmacokinetic study enrolling 10 Chinese patients with indolent B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia administered a single intravenous infusion of 100 mg m(2) bendamustine hydrochloride.
authors.affiliation: School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China.
authors.forename: Feifan
authors.initials: F
authors.lastname: Xie
authors.affiliation: School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China.
authors.forename: Zeneng
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Hunan Tiger-Xiangya R&D Company Ltd., Changsha 410013, PR China.
authors.forename: Hang
authors.initials: H
authors.lastname: Cheng
authors.affiliation: School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China. Electronic address: peng.yu@csu.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
mesh_terms: D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000652:urine*; D000069461:Bendamustine Hydrochloride; D002681:China; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000188:drug therapy / Q000652:urine; D016014:Linear Models; D016393:Lymphoma, B-Cell / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009588:Nitrogen Mustard Compounds / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000652:urine*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D018906:Antineoplastic Agents, Alkylating; D009588:Nitrogen Mustard Compounds; D000069461:Bendamustine Hydrochloride
keywords: Bendamustine; Gamma-hydroxy-bendamustine; HPLC-fluorescence detector; Human plasma; Pharmacokinetics