Neoplasma Vol.50, p.120-124, 2003
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Title: Rapid HPLC analysis of melphalan applied to hypertermic isolation limb perfusion
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Author: D., ROMANOVA
; J., NETRIOVA
; P., BOZEK
; Z., OVESNA
; K., KROUPA
; E., VALOVICOVA
; A, VACHALKOVA
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Abstract: Hyperthermic isolated limb perfusion (HILP) with melphalan (MH) as a standard
cytotoxic drug has been performed in 28 patients suffering from malignant
melanoma. MH has been administered by HILP via extracorporeal circulation
system. The drug given locoregionally reduces subsequent toxicity of organs. For
all that residues can leak into the systemic circulation during HILP. Because of
known carcinogenic potential and secondary cancer formation, the main interest
of this work is to determine MH concentration profile in the patient plasma
during and after HILP and evaluation of its potential toxicity in patients.
Reversed-phase HPLC assay, which uses isocratic elution and fluorimetric
detection has been shown to be sensitive, reliable and suitable for routine
analyses. The assay was validated for the concentration range of 50-2500 ng.ml-1
with the limit of detection (LOD) 6.881 ng.ml-1. The samples were treated by
methanol precipitation with the recovery more than 80%. The stability of
standard solutions and methanolic extracts of MH were also followed. The
concentration profile of MH in patient samples has been pursued in three time
points during and after chemoperfusion (45 min after application of MH in
extracorporeal circulation, 10 min after the joining the extremity to systemic
circulation and one hour after the great vessels reconstruction). The
concentrations of MH ranged 100-1500 ng.ml-1 and varied from patient-to-patient.
Some complications were observed after HILP in 11 patients and are correlated
with the higher con- centrations of MH (over 150 ng x ml-1) found in plasma.
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Keywords: Melphalan, hyperthermic osolation limb perfusion, malignant melanoma, isocratic HPLC, fluorescence detection.
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Year: 2003, Volume: 50, Issue: |
Page From: 120, Page To: 124 |
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