Concentrations of N-(phosphonacetyl)-L-aspartate (PALA) in plasma and tears in man.
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Antineoplastic Agents↗
Biomedical subjects
J Lankelma
Publications and source records attributed to J Lankelma.
Determination of 5-methyltetrahydrofolic acid in plasma and spinal fluid by high-performance liquid chromatography, using on-column concentration and electrochemical detection.
Chromatographic conditions for the determination of 5-methyltetrahydrofolic acid in plasma and spinal fluid are described, involving simple pretreatment of the sample. Electrochemical detection was used. The linear range of the method is more than 10(3). Recovery from plasma and spinal fluid is 100%, and the detection limit of the method is 2.10(-9) M, sufficient for the detection of endogenous plasma and spinal fluid levels. The detection conditions are discussed. Endogenous concentrations of the compound in plasma and spinal fluid were determined and correlated with a folate bioassay. Plasma concentrations have been shown after the administration of leucovorin which is used in anticancer therapy.
Animals↗
Determination of N-(phosphonacetyl)-L-aspartic acid (PALA) in plasma and urine by high pressure liquid chromatography.
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Aspartic Acid↗
The role of 7-hydroxymethotrexate during methotrexate anti-cancer therapy.
Plasma concentrations of 7-hydroxymethotrexate were measured in 10 individuals receiving methotrexate, 8 of them per infusion. After the end of infusion, the plasma concentration of formed 7-hydroxymethotrexate fell less rapidly than that of methotrexate. At 24 h after infusion, plasma concentration ratios of 7-hydroxymethotrexate ranged from 30 to 1 (n = 8). The presence of 7-hydroxymethotrexate was shown to influence the transport of methotrexate into Ehrlich ascites tumor cells and human KB cells, cultured in vitro. These findings suggest that monitoring of 7-OHMTX is important in MTX treatment.
Animals↗
Determination of methotrexate in plasma by on-column concentrations and ion-exchange chromatography.
A method for the concentration of dilute samples on a column and its application to the analysis of biomedical mixtures is described. Two columns are used, one for the concentration step and the other for the separation. The concentration column is used in the position of the loop in an injection valve. Concentration is effected by eluent switching. The influence of the chromatographic parameters such as capacity ratio and void volume on separation and detectability are described and the optimal choice of conditions is discussed. The method has been applied to the analysis of the cytostatic drug methotrexate. An octyl-modified silica was used as the stationary phase in the concentration column and a chemically bonded anion exchanger on silica in the separation column. The procedure shows good selectivity and precision. The detection limit corresponds to 2.10-8 M (9 ppb) in plasma, which is sufficiently low for therapeutic concentrations to be measured. An example of the use of the same stationary phase in both columns is given for the analysis of phenothiazines in blood, using alkyl-modified silica and electrochemical detection.
Chromatography, Ion Exchange↗
Anodic coulometric detection with a glassy carbon electrode in combination with reversed-phase high-performance liquid chromatography. Determination of blood levels of perphenazine and fluphenazine.
A detector for liquid chromatography, based on anodic electrochemical oxidation at a glassy carbon electrode, is used in combination with reversed-phase liquid chromatography for the determination of the long-acting tricyclic psychotropic drugs fluphenazine and perphenazine in blood. Completely porous microparticulate silica material, modified so as to give a methyl silica, was used as the stationary phase and buffered mixtures of methanol and water as the mobile phase. The low detection limit and the selectivity of the coulometric detector made possible the determination of concentrations of 1-20 ppb of the compounds of interest. An extraction procedure was in order to obtain sufficient selectivity. Data for the precision, detection limit and yield of the extraction procedure are given. A number of serum levels of perphenazine after oral administration and of fluphenazine after i.m. doses of fluphenazine decanoate are stated.
Carbon↗
Change in transfer rate of methotrexate from spinal fluid to plasma during intrathecal therapy in children and adults.
Methotrexate plasma concentrations were measured repeatedly over 48 hours after each of 5 subsequent intrathecal injections in 14 children and 8 adult patients with acute lymphoblastic leukaemia. Two patterns of concentration profiles were distinguished: a) The plasma concentration reached a rather low maximum, followed by a relatively slow decline ('slow type'): b) The plasma concentration increased rapidly to a relatively high value after which it declined rather steeply ('fast type'). The incidence of the 'fast type' increased progressively with the number of intrathecal injections. When the plasma concentration-time curves were described by a pharmacokinetic 2-compartment open model with first-order absorption, it was calculated that the transfer of methotrexate from the spinal fluid into the plasma is much slower for the 'slow type' compared with the 'fast type'. Assuming concentration-dependent cytostatic activity, the therapeutic efficacy in the central nervous system is likely to be less for the 'fast type' than for the 'slow type'. Systemic toxicity resulting from the 'slow type' is expected to be higher than from the 'fast type'.
Adolescent↗
Diurnal variation in the therapeutic efficacy of 5-fluorouracil against murine colon cancer.
Mice bearing the murine colon carcinomas Colon 38 or Colon 26 were treated with 5-fluorouracil (5 FU) (60 or 100 mg/kg, respectively) weekly for 4 weeks at 08.30 hr or at 18.30 hr. The antitumor effect of treatment at 08.30 hr was significantly better for both types of tumors, but most pronounced for Colon 38. Toxicity was evaluated after administration of 60 mg 5 FU/kg. No thrombocytopenia was observed. Leucopenia was observed after treatment at 18.30 hr. It is concluded that the therapeutic efficacy of 5 FU against murine colon cancer is higher when 5 FU is administered at 08.30 hr.
Animals↗
High uridine phosphorylase activity in human melanoma tumor.
Uridine (Urd) phosphorylase and Urd kinase activities were examined in 4 human tumor types including melanoma and human and mouse melanoma cell lines. Urd phosphorylase activity in melanoma tumor specimens was higher than in specimens of colon, ovarian, and breast tumors. Urd kinase activity levels were similar in the 4 tumor types. In 3 human melanoma cell lines examined, Urd phosphorylase activity was markedly greater than in mouse B16 melanoma cells, while Urd kinase activity did not differ appreciably in the human and mouse cell lines. Urd phosphorylase activity in crude extract preparations from different melanoma cell lines showed similar substrate affinity and sensitivity to 1-(2'-deoxy-beta-D-glucopyranosyl)-thymine, a specific inhibitor. The high Urd phosphorylase activity found in melanoma tumor tissue may be exploited in the treatment of malignant melanoma with antipyrimidine agents. Cultured human melanoma cells retain this biochemical characteristic and may serve as appropriate in vitro models for the human tumor in studies concerning pyrimidine metabolism.
Animals↗