RP-LC determination of 5-fluorouridine in nanoparticulate formulations.
5-fluorouridine (5-FUrd) is an anticancerous drug with a number of side effects due to its high toxicity. One possibility to overcome these drawbacks may consist on the use of polymeric nanoparticles to increase the therapeutic index of this drug. The objective of this study was to develop an analytical high performance liquid chromatography (HPLC) method for the determination of (i) the 5-FUrd content in poly (methyl vinyl ether-co-maleic anhydride) nanoparticles, (ii) its release from these carriers and, its eventual degradation during preparation, storage or release in 5-fluorouracil (5-FU). The chromatography was performed on a reversed-phase encapped column (LiChrospher Select B C8) with a mobile phase of 0.05 M ammonium acetate (pH 6.5). Ganciclovir (GCV) was used as internal standard and the detection wavelength was 268 nm. The limits of quantification of 5-FUrd and 5-FU were 12 and 5 ng/ml, respectively. Similarly, precision did not exceed 7%. Under our experimental conditions, the maximal drug loading capacity of 5-FUrd was around 105 microg/mg nanoparticle and the drug was released in a biphasic way from these particles. In addition, no degradation of 5-FUrd to 5-FU during either the preparative process or the release studies was observed. In summary, this HPLC method is selective, sensitive, specific and reproducible for the quantification of 5-FUrd in polymeric nanoparticles and release mediums.
Arbós
P
P
Centro Galénico, Universidad de Navarra, Aptdo. 177, C/Irunlarrea s/n, 31080, Navarra, Pamplona, Spain.
Campanero
M A
MA
Irache
Juan M
JM
D000970:Antineoplastic Agents / Q000032:analysis*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D005472:Fluorouracil / Q000032:analysis; D015203:Reproducibility of Results; D012996:Solutions; D014529:Uridine / Q000031:analogs & derivatives* / Q000032:analysis*
D000970:Antineoplastic Agents; D012996:Solutions; C001943:5-fluorouridine; D005472:Fluorouracil; D014529:Uridine