RESUMO
Objective: To instruct a method of determining thallium in the urine by graphite furnace atomic absorption spectrometry(GF-AAS) with colloidal palladium as the matrix modifier. Methods: Urine samples were first diluted and then determined by GF-AAS with colloidal palladium while using thermal sample injection. Results: The optimum volume of colloidal palladium was 6 µl and the best ashing temperature was 600-800 â while the atomization temperature was 1700-1900 â . This method showed a good linearity relationship when the concentration between 0.33 and 50.0 µg/L while the correlation coefficient of standard curve line was 0.9992, and the detection limit was 0.33 µg/L and the recovery rate was between 92.7% and 102.3% with the intra-day precision in the range of 2.55% to 3.66% and the inter-day precision in the range of 1.77% to 3.85%. Conclusion: This method has the advantages of low detect limit, high sensitivity and good precision, and it can be used in the biological monitoring and emergency detecting of workers exposed to thallium.
Assuntos
Tálio/urina , Protocolos de Quimioterapia Combinada Antineoplásica/análise , Ciclofosfamida/análise , Grafite , Humanos , Limite de Detecção , Lomustina/análise , Paládio , Espectrofotometria Atômica , Vincristina/análiseRESUMO
The effects of solvent dipolarity/polarizability and solvent-solute hydrogen bonding on the photophysical properties of the antineoplastic drug lomustine were analysed by means of the linear solvation energy relationship (LSER) concept proposed by Kamlet and Taft. The LSER method enabled the overall solvent effects to be quantitatively estimated and separated into specific and non-specific contributions. The molecular encapsulation of lomustine by ß-cyclodextrin (ß-CD) has been studied using fluorescence spectroscopy. The results are discussed in terms of the binding parameter and the effect of the solvent used. It was concluded that ß-CD forms a 1:1 inclusional complex with lomustine in acetonitrile solution and its association constant was calculated to be 500 M(-1). In addition, and for the first time, a simple, rapid and high sensitive fluorimetric method for the determination of lomustine was developed based upon the enhancement effect produced through complex formation with ß-CD. The new approach for the quantification of lomustine in the presence of ß-CD was described in aqueous and organic solutions. Better limits of detection (0.31 µg ml(-1)) and quantification (1.05 µg ml(-1)) were obtained in aqueous solution with respect to those obtained in organic solvent.
Assuntos
Antineoplásicos/análise , Lomustina/análise , beta-Ciclodextrinas/química , Espectrometria de FluorescênciaRESUMO
To study the pharmacokinetics of the novel lomustine liposome, a specific, simple, and reliable high-performance liquid chromatography with ultraviolet detection (HPLC/UV) method for quantification of lomustine in rat plasma was established and validated. The calibration curve was linear over the concentration range of 0.05-5 µg/mL with the linearity (r (2)) being ≥0.9994. The intra- and inter-day precision was less than 5.87 and 10.47%, respectively, and the accuracy was within ±7.95%. The validated method has been successfully applied to a pharmacokinetic study of thermosensitive liposome-encapsulated lomustine containing iohexol and lomustine solution after intravenous administration to C6 glioma rats. Population pharmacokinetic (PPK) analysis was performed using NONMEM program for the plasma concentration versus time data. A one-compartment model with first-order elimination was established and proved to be the best description of the lomustine profile. Bootstrap analysis (n = 1,000) was executed to evaluate the stability and robustness of the model. The pharmacokinetic parameters of lomustine liposome containing iohexol and lomustine solution in rats were simulated using the final PPK model: t (1/2), AUC(0-∞), C (max) were 0.28 ± 0.12, 0.19 ± 0.08, and 0.30 ± 0.13 h; 2.37 ± 0.76, 1.32 ± 0.42, and 0.90 ± 0.29 mg h/L; 5.15 ± 2.22, 3.91 ± 1.90, and 1.87 ± 0.35 µg/mL for heated, non-heated, and control group, respectively. The result indicated that thermosensitive liposome-encapsulated lomustine containing iohexol for CT imaging had different pharmacokinetic characteristics than lomustine solution. Compared with non-heated group, the bioavailability of lomustine was obviously increased in C6 glioma rat plasma.
Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Neoplasias Encefálicas/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Glioma/diagnóstico por imagem , Iohexol/administração & dosagem , Lipossomos , Lomustina/administração & dosagem , Lomustina/farmacocinética , Animais , Antineoplásicos/análise , Área Sob a Curva , Calibragem , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Portadores de Fármacos , Composição de Medicamentos , Injeções Intravenosas , Lomustina/análise , Modelos Estatísticos , Controle de Qualidade , Ratos , Reprodutibilidade dos Testes , Espectrofotometria Ultravioleta , Tomografia Computadorizada por Raios XRESUMO
A simple, inexpensive and rapid liquid chromatography (LC) method has been developed for the quantitative determination of Lomustine, an chemotherapy drug. Degradation studies were performed on the bulk drug by heating to 60 °C, exposure to UV light at an energy of 200 Wh/m(2)and to visible light at an illumination of not less than 1.2 million lux hours, acid (0.1N hydrochloric acid), base (0.1N sodium hydroxide) aqueous hydrolysis and oxidation with 6.0% (v/v) hydrogen peroxide. Good resolution between the peaks corresponding to impurities produced during synthesis, degradation products and the analyte was achieved on a Symmetry C 8 LC column using a mobile phase consisting of a mixture of aqueous potassium dihydrogen phosphate and acetonitrile. The degradation samples were assayed against the reference standard of Lomustine and the mass balance in each case was close to 99.9%. Validation of the method was carried out as per International Conference on Harmonization (ICH) requirements.
Assuntos
Química Farmacêutica/métodos , Cromatografia Líquida/métodos , Lomustina/análise , Acetonitrilas/química , Técnicas de Química Analítica , Cromatografia/métodos , Estabilidade de Medicamentos , Peróxido de Hidrogênio/química , Hidrólise , Lomustina/química , Modelos Químicos , Reprodutibilidade dos Testes , Temperatura , Raios UltravioletaRESUMO
This paper reports a RP-HPLC method for the determination of Lomustine (CCNU) in mouse tumor tissue. CCNU was separated and determined on a reverse-phase C18 5 microm column with a mobile phase of H2O-acetonitrile (54:46), detected at 254 nm and no internal standard. The calibration curve was linear (r = 0.9999) within the range of 0.98-15.68 microg/ml for CCNU. The recovery ratio of CCNU was 68.64% (n = 5). The relative standard deviation (RSD) was 0.32%. This method is simple and accurate.
Assuntos
Antineoplásicos Alquilantes/análise , Lomustina/análise , Sarcoma/química , Animais , Antineoplásicos Alquilantes/administração & dosagem , Cromatografia Líquida de Alta Pressão/métodos , Lomustina/administração & dosagem , Masculino , Camundongos , Sarcoma/tratamento farmacológicoRESUMO
An expedient, rapid, and sensitive capillary gas chromatographic method for the analysis of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in plasma is described. Separation of the underivatized nitrosourea compounds was performed on a 0.33-mm-i.d., 25-m fused-silica, SE-30 capillary column, and detection was carried out using a thermionic N-P-specific detector. The compounds were extracted from plasma with benzene with a yield of greater than 87%. The assay was linear in the ranges of 0.001 to 0.5 and 0.5 to 25 micrograms/ml for CCNU or 0.003 to 0.50 and 0.5 to 25 micrograms/ml for BCNU, with correlation coefficients from 0.9914 to 0.9999 and coefficients of variation (CV) of less than 3.3%. Other antineoplastic agents did not interfere in the assay. The method was employed to study the pharmacokinetics of BCNU in rabbits. The plasma concentration-time curves were fit to a two-compartment model with a mean (SE) alpha, beta, and total-body clearance of 2.898 (0.913) hr-1, 0.1228 (0.0179) hr-1, and 7.211 (2.862) liters/hr.kg, respectively. Further, the stability of BCNU and CCNU in solution was examined at different temperatures. Both compounds were stable in benzene or acetone (4 to 37 degrees C) but labile in plasma even if refrigerated. The apparent rate constants for degradation of BCNU and CCNU were 0.09921 and 0.02853 hr-1 at 4 degrees C and 5.998 and 2.553 hr-1 at 37 degrees C, respectively.
Assuntos
Carmustina/análise , Lomustina/análise , Animais , Calibragem , Carmustina/farmacocinética , Cromatografia Gasosa/instrumentação , Cromatografia Gasosa/métodos , Estabilidade de Medicamentos , Lomustina/farmacocinética , Coelhos , Reprodutibilidade dos TestesRESUMO
A formulation of 14C-lomustine in propylene glycol-ethanol (4:1) was administered intravenously to rats infiltrated with glioma tumors of the astrocytic series (RT6). The organ and tumor distribution of this agent was followed at 1, 4, 12, and 24 hr. Rapid blood disappearance (0-1 hr) of the label concomitant with an increase in all organs except the lung, muscle, and brain was observed. Only the blood, liver, and muscle contained greater than 1% of the dose after 24 hr. The bladder, liver, small bowel, and kidneys concentrated the highest percentages throughout the study. The distribution of 14C-lomustine in the tumor relative to the brain, muscle, and blood showed a maximum 4-12 hr after administration.