Improved methodology for subnanogram quantitation of doxorubicin and its 13-hydroxy metabolite in biological fluids by liquid chromatography

✍ Scribed by David T. Rossi; Barbara A. Phillips; John R. Baldwin; Prem K. Narang

• Publisher: Elsevier Science
• Year: 1993
• Tongue: English
• Weight: 801 KB
• Volume: 271
• Category: Article
• ISSN: 0003-2670
• DOI: 10.1016/0003-2670(93)80552-v

✦ Synopsis

Sensltwe and speafic methodology for quant&mg doxorublcm (DOX), a potent antmeoplastlc drug, and Its 13-hydroxy metabohte, doxorublcmol (DOX-OL), m plasma and urme has been developed and vahdated The plasma method uses sohd-phase extractlon for analyte lsolatlon and a narrow-bore (2 0 mm Ed) column for hqmd chromatographlc separation Hrlth optlmlzed fluorescence detectlon The dynanuc ranges for both drug and metabohte m plasma are hnear from 0 2 to 100 ng ml-' Drug and metabohte are quantified m unextracted, dduted urme over a 16 to 400 ng ml-' range Epuublcm, an epunenc analogue of doxorublcm, IS used as an Internal standard Mean extraction efficlencles for drug, metabohte and Internal standard from plasma are 88, 86 and 90%, respectively The mstmmental detection hnut (sIgnal-to-noise ratlo = 3) for doxorublcm or metabohte was 18 pg on column, whde the lower hnut of quantitatlon (LLOQ) was 0 3 and 0 6 ng ml-', respectwely for DOX and DOX-OL The typical mtra-day accuracy and ImprecIsIon m plasma was < 8% bias and < 9% relative standard devlatlon (R S D ) for DOX at or above 0 3 ng ml-', and < 15% and < 10% for DOX-OL at or above 0 6 ng ml-' For the urme method, the average mtra-day lmpreclslon was < 7% R S D and the average bms was < 5% for both drug and metabohte over the entlre dynamic range Determmatlons of these two components m patlent samples has verdied the robustness and utlhty of the method