Simple high-performance liquid chromatographic assay for melphalan in perfusate, rat liver and tumour tissue.
A simple, sensitive and selective reversed-phase liquid chromatographic assay has been developed and validated for the anti-cancer agent melphalan in perfusate, liver and tumour tissue originating from isolated rat liver perfusion studies. Melphalan was extracted from the matrix using ice-cold methanol. The drug and the internal standard, propylparaben, were detected using ultraviolet absorbance at 262 nm. The assay has been validated in the 0.05-25 microg/mL range for perfusate; the lower limit of quantification (LLQ) is 0.05 microg/mL in perfusate and 0.25 ng/mg in liver and tumour tissues. Accuracies ranged from 89 to 110% and the inter-assay precisions were all below 15% (20% at the LLQ). Melphalan in a biological matrix has to be processed between 0 and 4 degrees C and is stable under all relevant processing and storage conditions tested. The assay has been exhaustively used in isolated liver perfusion studies with the drug demonstrating its applicability.
Sparidans
Rolf W
RW
Faculty of Pharmaceutical Sciences, Department of Biomedical Analysis, Division of Drug Toxicology, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands. R.W.Sparidans@pharm.uu.nl
Silvertand
Linda
L
Dost
Frits
F
Rothbarth
Joost
J
Mulder
Gerard J
GJ
Schellens
Jan H M
JH
Beijnen
Jos H
JH
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008099:Liver / Q000737:chemistry*; D008114:Liver Neoplasms, Experimental / Q000737:chemistry*; D008297:Male; D008558:Melphalan / Q000032:analysis*; D010477:Perfusion; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan