title: LC-MS/MS method development for quantification of doxorubicin and its metabolite 13-hydroxy doxorubicin in mice biological matrices: Application to a pharmaco-delivery study.
abstract: This study describes the development of simple, rapid and sensitive liquid chromatography tandem mass spectrometry method for the simultaneous analysis of doxorubicin and its major metabolite, doxorubicinol, in mouse plasma, urine and tissues. The calibration curves were linear over the range 5-250 ng/mL for doxorubicin and 1.25-25 ng/mL for doxorubicinol in plasma and tumor, over the range 25-500 ng/mL for doxorubicin and 1.25-25 ng/mL for doxorubicinol in liver and kidney, and over the range 25-1000 ng/mL for doxorubicin and doxorubicinol in urine. The study was validated, using quality control samples prepared in all different matrices, for accuracy, precision, linearity, selectivity, lower limit of quantification and recovery in accordance with the US Food & Drug Administration guidelines. The method was successfully applied in determining the pharmaco-distribution of doxorubicin and doxorubicinol after intravenously administration in tumor-bearing mice of drug, free or nano-formulated in ferritin nanoparticles or in liposomes. Obtained results demonstrate an effective different distribution and doxorubicin protection against metabolism linked to nano-formulation. This method, thanks to its validation in plasma and urine, could be a powerful tool for pharmaceutical research and therapeutic drug monitoring, which is a clinical approach currently used in the optimization of oncologic treatments.
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco", Università degli Studi di Milano, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Mazzucchelli
authors.affiliation: Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Sezione di Tossicologia Forense, Università degli Studi di Milano, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ravelli
authors.affiliation: Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Sezione di Tossicologia Forense, Università degli Studi di Milano, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Gigli
authors.affiliation: Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Sezione di Tossicologia Forense, Università degli Studi di Milano, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Minoli
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco", Università degli Studi di Milano, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Corsi
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco", Università degli Studi di Milano, Italy.
authors.forename: Pierangela
authors.initials: P
authors.lastname: Ciuffreda
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco", Università degli Studi di Milano, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ottria
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D057230:Limit of Detection; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: C000615702:13-hydroxydoxorubicin; D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D004317:Doxorubicin; C010013:adriamycinol
keywords: LC-MS/MS; doxorubicin; doxorubicinol; nano-formulated drug; quantification