High-performance liquid chromatographic assay for melphalan in human plasma. Application to pharmacokinetic studies.
This paper describes a simple, rapid and reproducible high-performance liquid chromatographic method (HPLC) with ultraviolet absorbance detection for the analysis of melphalan in plasma. The HPLC column was an Ultrasphere ODS (5 microns) and the eluent was composed of methanol, purified water and acetic acid (49.5:49.5:1, v/v). The detection was performed at 261 nm. The method involved a simple treatment of the samples with methanol. The propylparaben was used as internal standard. Linear detection response was obtained for concentrations ranging from 50 to 2500 ng/ml. Recovery from plasma proved to be more than 90%. Precision, expressed as C.V., was in the 0.5 to 9% range. Accuracy ranged from 95 to 102%. This method was used to determine the pharmacokinetic parameters of melphalan following high-dose (140 mg/m2) intravenous administration in patients with advanced malignancies undergoing peripheral blood hematopoietic progenitor-cell transplantation.
Pinguet
F
F
Laboratoire d'Onco-Pharmacologie, Centre Régional de Lutte contre le cancer, Montpellier, France.
Joulia
J M
JM
Martel
P
P
Grosse
P Y
PY
Astre
C
C
Bressolle
F
F
D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002940:Circadian Rhythm; D004355:Drug Stability; D006801:Humans; D007275:Injections, Intravenous; D016014:Linear Models; D008558:Melphalan / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D010226:Parabens / Q000032:analysis / Q000737:chemistry; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
D018906:Antineoplastic Agents, Alkylating; D010226:Parabens; D008558:Melphalan; C006068:propylparaben