title: An eco-friendly stability-indicating spectrofluorimetric method for the determination of two anticancer stereoisomer drugs in their pharmaceutical preparations following micellar enhancement: Application to kinetic degradation studies.
abstract: A new rapid and highly sensitive stability-indicating spectrofluorimetric method was developed for the determination of two stereoisomers anticancer drugs, doxorubicin (DOX) and epirubicin (EPI) in pure form and in pharmaceutical preparations. The fluorescence spectral behavior of DOX and EPI in a sodium dodecyl sulfate (SDS) micellar system was investigated. It was found that the fluorescence intensity of DOX and EPI in an aqueous solution of phosphate buffer pH4.0 and in the presence of SDS was greatly (about two fold) enhanced and the mechanism of fluorescence enhancement effect of SDS on DOX was also investigated. The fluorescence intensity of DOX or EPI was measured at 553nm after excitation at 497nm. The plots of fluorescence intensity versus concentration were rectilinear over a range of 0.03-2μg/mL for both DOX and EPI with good correlation coefficient (r>0.999). High sensitivity to DOX and EPI was attained using the proposed method with limits of detection of 10 and 9ng/mL and limits of quantitation of 29 and 28ng/mL, for DOX and EPI, respectively. The method was successfully applied for the determination of DOX and EPI in biological fluids and in their commercial pharmaceutical preparations and the results were concordant with those obtained using a previously reported method. The application of the proposed method was extended to stability studies of DOX following different forced degradation conditions (acidic, alkaline, oxidative and photolytic) according to ICH guidelines. Moreover, the kinetics of the alkaline and oxidative degradation of DOX was investigated and the apparent first-order rate constants and half-life times were calculated.
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Analytical Chemistry, University of Alexandria, El-Messalah, Alexandria 21521, Egypt. Electronic address: eman_elkimary@yahoo.com.
authors.forename: Eman I
authors.initials: EI
authors.lastname: El-Kimary
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Analytical Chemistry, University of Alexandria, El-Messalah, Alexandria 21521, Egypt.
authors.forename: Amira F
authors.initials: AF
authors.lastname: El-Yazbi
mesh_terms: D000143:Acids / Q000737:chemistry; D000328:Adult; D000468:Alkalies / Q000737:chemistry; D000970:Antineoplastic Agents / Q000032:analysis* / Q000097:blood / Q000737:chemistry* / Q000652:urine; D002626:Chemistry, Pharmaceutical; D004317:Doxorubicin / Q000032:analysis* / Q000097:blood / Q000737:chemistry / Q000652:urine; D015251:Epirubicin / Q000032:analysis* / Q000097:blood / Q000737:chemistry / Q000652:urine; D055772:Green Chemistry Technology / Q000379:methods*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D057230:Limit of Detection; D046911:Macromolecular Substances / Q000737:chemistry; D008297:Male; D008823:Micelles; D010084:Oxidation-Reduction; D015203:Reproducibility of Results; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012997:Solvents; D013050:Spectrometry, Fluorescence / Q000379:methods*; D013237:Stereoisomerism; D013501:Surface-Active Agents / Q000737:chemistry; D013997:Time Factors
chemical_list: D000143:Acids; D000468:Alkalies; D000970:Antineoplastic Agents; D046911:Macromolecular Substances; D008823:Micelles; D012997:Solvents; D013501:Surface-Active Agents; D012967:Sodium Dodecyl Sulfate; D015251:Epirubicin; D004317:Doxorubicin
keywords: Doxorubicin; Epirubicin; Micelle-enhanced; Pharmaceutical preparations; Stability-indicating