Determination of amphotericin B in rat blood plasma. Comparison of antifungal activity and pharmacokinetics profile of conventional amphotericin B and its conjugate with poly(ethylene glycol)
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Determination of amphotericin B in rat blood plasma. Comparison of antifungal activity and pharmacokinetics profile of conventional amphotericin B and its conjugate with poly(ethylene glycol)
Zdrojový dokument:Scientific papers of the University of Pardubice. Series A, Faculty of Chemical Technology. 18/2012
ISSN:1211-5541
Abstrakt:
New intravenous non-covalent conjugate of amphotericin B (AMB)-poly(ethylene
glycol)(PEG) (M = 10 000 g mol–1) is described. This well water soluble conjugate
contains 4 % (w/w) free AMB. A simple and sensitive HPLC-UV method was
developed and validated for the quantification of free amphotericin B in rat
plasma. A simple mobile phase consisting of 10 mM ammonium acetate (pH 3.60)
and acetonitrile (56:44, v/v) was pumped at a flow rate of 0.3 ml min–1 through a
reverse phase column maintained at 30 °C. Rifampicin was used as an internal
standard (IS). Rapid sample preparation involved the addition of 500 µl
acetonitrile-methanol mixture and 10 µl IS to 200 µl plasma to precipitate plasma proteins. Supernatant was evaporated to dryness under the stream of nitrogen and
dissolved in 125 µl of the mobile phase and injected onto column. The procedures
were validated within the linear concentration range from 0.06 to 2.5 µg ml–1 with
good reproducibility and linear response (r2 = 0.9988). The method described is
cost-effective and has necessary accuracy and precision for the rapid quantitative
determination of AMB in rat plasma. A two-compartment model described the
plasma drug concentration-time profiles.