title: Simultaneous measurement of doxorubicin and reduced metabolite doxorubicinol by UHPLC-MS/MS in human plasma of HCC patients treated with TACE.
abstract: A sensitive, selective, accurate and precise method for simultaneous quantification of doxorubicin (DOX) and doxorubicinol (DOXol) in human plasma of patients diagnosed as having intermediate stage unresectable hepatocellular carcinoma (HCC) was developed. The method was based on electrospray tandem mass spectrometry in selected reaction monitoring mode. DOX, DOXol and trofosfamide, an internal standard, were extracted from plasma by using a simple solid phase extraction (SPE) procedure after the addition of 0.1 M hydrochloric acid. A 200-μL aliquot of the extracted sample reconstituted in mobile phase was analyzed on a Zorbax SB-C18 UHPLC column (50 mm × 2.1 mm, 1.8 μm particle size) in 8 min. The mobile phase consisted of acetonitrile and 0.1% formic acid pH 4.5 (95:05 v/v). Good accuracy and precision of this method were demonstrated by determination of spiked plasma QC samples in four consecutive days. The SPE extraction recoveries ranged from 72.3 to 77.3% and 75.5 to 98.4% for doxorubicin and doxorubicinol, respectively. The intra-day and inter-day precisions were less than 11.4%. The limit of quantitation was 1.0 ng/mL for both compounds. The calibration curves of DOX and DOXol were analyzed by weighted linear regression with 1/x as a weighting factor. They were linear over the concentration range of 1.0-100.0 ng/mL with R(2) greater than 0.99. This developed method was successfully applied to study plasma pharmacokinetics in patients affected by HCC and treated with transarterial chemoemolization practices (TACEs) using HepaSphere™ pre-loaded with DOX in a standardized procedure.
authors: Laboratory for Environmental and Toxicological Measurements, IRCCS Pavia, S. Maugeri Foundation, via S. Maugeri 10, Pavia, Italy. cristina.sottani@fsm.it
authors: Cristina
authors: C
authors: Sottani
authors: Guido
authors: G
authors: Poggi
authors: Fabio
authors: F
authors: Melchiorre
authors: Benedetta
authors: B
authors: Montagna
authors: Claudio
authors: C
authors: Minoia
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D004355:Drug Stability; D006801:Humans; D016014:Linear Models; D008113:Liver Neoplasms / Q000097:blood / Q000628:therapy*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D004317:Doxorubicin; C010013:adriamycinol