-
[show abstract]
[hide abstract]
ABSTRACT: 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.
Journal of chromatography. B, Biomedical applications 12/1996; 686(1):43-9.
-
[show abstract]
[hide abstract]
ABSTRACT: Prolonged infusions of 5-fluorouracil (5FU) have been used since the early 1960s, but recently there has been a major resurgence of interest, partly because of the advent of electronically controlled portable infusion pumps. Admixtures of new formulation 5FU were subjected to stability studies to establish the feasability of continuous infusions. In the first study, the stability of 5FU, 1 or 10 mg ml(-1), was determined in poly(vinyl chloride) (PVC) bags (0.9% sodium chloride injection or 5% dextrose injection) at 4 and 21 degrees C after storage for 0, 1, 2, 3, 4, 7 and 14 days. In the second study, the stability of undiluted 5FU was tested at different temperatures (4 or 33 degrees C) in ethylene-vinyl acetate (EVA) or PVC ambulatory pump reservoirs after storage for 0, 3, 5, 7 and 14 days. For each condition, samples from each admixture were tested for drug concentration by stability-indicating high-performance liquid chromatography. The admixtures were also monitored for precipitation, colour change and pH. Evaporative water loss from the containers was measured. The stability of 5FU in PVC bags was unaffected by 14 days of storage at either 4 or 21 degrees C. When stored in EVA reservoirs, 5FU was stable for at least 2 weeks at 33 degrees C and for 3 days at 4 degrees C (a precipitate was observed after 3 days). In PVC reservoirs, 5FU was stable for over 14 days at 33 degrees C, but at 4 degrees C a precipitate appeared after 5 days. Loss of water through the reservoirs was substantial only at 33 degrees C for 14 days, and gave falsely high readings.
Journal of Pharmaceutical and Biomedical Analysis 03/1996; 14(4):395-9. · 2.97 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This paper describes a high-performance liquid chromatographic method (HPLC) with fluorometric detection for the analysis of granisetron in plasma. The detection is performed at 305 nm for excitation and 365 nm for emission. The method involves sample clean-up by liquid-liquid extraction. N-(1-Naphthyl) ethylenediamine dihydrochloride is used as internal standard. Toluene and phosphate buffer were added to 0.5 ml of plasma added to the internal standard. After extraction, the organic layer was separated and then evaporated to dryness. The residue was reconstituted in eluent mixture. An aliquot was injected onto the HPLC column, Spherisorb CN, equilibrated with an eluent mixture constituted by acetonitrile-phosphate buffer (pH 4.5) (15:85). The proposed technique is reproducible, selective, reliable, and sensitive. Linear detector responses were observed for the calibration curve standards in the range of 0.50 to 100 ng/ml. Extraction recovery from plasma proved to be more than 90%. Precision expressed as C.V. was in the range 2 to 8%. As low as 0.3 ng of granisetron per ml of plasma can be measured with good accuracy. The method has been validated, and stability tests under various conditions have been performed. Its sensitivity is adequate for pharmacokinetic studies.
Journal of chromatography. B, Biomedical applications 02/1996; 675(1):99-105.
-
Journal of Pharmaceutical Sciences 03/1995; 84(2):267-8. · 3.06 Impact Factor
-
American journal of hospital pharmacy 12/1994; 51(21):2701-4.
-
[show abstract]
[hide abstract]
ABSTRACT: The pharmacokinetics of melphalan following high-dose (140 mg/m2) i.v. administration were determined in 20 patients with advanced malignancies undergoing peripheral blood hematopoietic progenitor-cell transplantation. Melphalan was assayed in plasma by a specific HPLC method with UV detection. Plasma levels of melphalan declined in a biexponential fashion with a mean terminal half-life of 83 minutes (range 52-168 minutes). Estimated peak plasma concentrations ranged from 1.65 to 14.5 micrograms/ml. Plasma levels were lower than the limit of quantitation of the method used (20 ng/ml) 24 hours after drug administration. The average volume of distribution and total clearance were 317 ml/min/m2 (range 127-797 ml/min/m2) and 37.9 l/m2 (range 15.4-108 l/m2), respectively. These parameters are similar to those reported in the literature. A weak correlation was found between total clearance of melphalan and creatinine clearance (p < 0.05). No relationship between the pharmacokinetics of melphalan and myelosuppression and non-hematologic toxicities was recovered. This pharmacokinetic study indicates that on the assumption that there is no more circulating melphalan after seven elimination half-lives, it may be possible to reinfuse autologous PBPC 10-20 hours after melphalan administration.
Anticancer research 17(1B):605-11. · 1.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A major obstacle in efficacy of breast cancer chemotherapy is the emergence of multidrug resistance. We investigated modulation of multidrug resistance by liposome-encapsulated mitoxantrone in a drug resistant human breast MCF7R cell line and the influence of liposome composition. Neutral high phase-transition temperature and anionic low phase-transition temperature phospholipid liposomes, reduced the resistance factor from 142 to 15 and 38, respectively. The higher cytotoxicity obtained with mitoxantrone-encapsulation was not necessarily related to higher intracellular uptake. Our data suggest that liposomes, according to their lipid composition, may alter the P-glycoprotein function by plasma membrane stabilization and modulate multidrug resistance in human cancer.
Anticancer research 19(4B):3327-31. · 1.73 Impact Factor
