RESUMO
The kinetics of degradation of the new anti-tumor drug, 4-dedimethylamino sancycline (col-3) in aqueous solution at 25oC were investigated by high-pressure liquid chromatography (HPLC) over the pH-range of 2-10. The influences of pH, buffer concentration, light, temperature, and some additives on the degradation rate were studied. The degradation of col-3 was found to follow first order kinetics. A rate expression covering the degradation of the various ionic forms of the drug was derived and shown to account for the shape of the experimental pH-rate profile. Under basic conditions, the degradation of col-3 involves oxidation, which is catalyzed by metal ions and inhibited by EDTA and Sodium bisulfite.
Assuntos
Antibióticos Antineoplásicos/química , Tetraciclina/química , Soluções Tampão , Catálise , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Cinética , Luz , Fotoquímica , Soluções , Temperatura , Tetraciclinas , Água/químicaRESUMO
A spectrophotometric technique was used to determine the acidity constants of 4-dedimethylamino sancycline (Col-3), a new antitumor drug. The apparent pKa values of Col-3 in 0.5% methanol aqueous media at approximately 25 degrees C with a constant ionic strength of 0.2 were calculated manually and graphically to be 5.64 +/- 0.17 (pKa1) and 8.35 +/- 0.07 (pKa2). In addition, the computer program SQUAD was used to confirm Col-3 pKa values. The pKa values obtained by SQUAD were pKa1 5.63 +/- 0.14 and pKa2 8.39 +/- 0.04. These results are in agreement with the tetracycline-like structure of Col-3.
Assuntos
Antineoplásicos/química , Tetraciclina/química , Concentração de Íons de Hidrogênio , Espectrofotometria , TetraciclinasRESUMO
A solid-phase extraction (SPE) method has been developed for the isolation of melanotan II from rabbit urine. The proposed extraction method makes it possible to selectively isolate melanotan II without significant loss of the peptide. Standard curves obtained from high-performance liquid chromatographic (HPLC) analysis of spiked urine extracts are linear from 0.1 to 4.0 micrograms/ml. The analytical method is shown to be highly reproducible, giving a relative standard deviation of less than 5% for both between-day and same-day analyses. The accuracy of the method obtained from standard plots ranges from -3.3 to 3.1%.
Assuntos
Anticarcinógenos/urina , Peptídeos Cíclicos/urina , alfa-MSH/análogos & derivados , Animais , Cromatografia Líquida de Alta Pressão/métodos , Coelhos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , alfa-MSH/urinaAssuntos
Anticarcinógenos/administração & dosagem , Peptídeos Cíclicos/administração & dosagem , alfa-MSH/análogos & derivados , Animais , Anticarcinógenos/urina , Disponibilidade Biológica , Sistemas de Liberação de Medicamentos/métodos , Feminino , Esponja de Gelatina Absorvível , Instilação de Medicamentos , Masculino , Soluções Oftálmicas , Peptídeos Cíclicos/urina , Coelhos , alfa-MSH/administração & dosagem , alfa-MSH/urinaRESUMO
Injectable and infusion formulations of dexverapamil are evaluated for their potential to produce phlebitis. The evaluation technique utilizes two independent in vitro methods and two in vivo methods to screen a pH solubilized drug for its potential to induce phlebitis due to precipitation at the injection site. One method is based upon a theoretical calculation that simulates the change of solubility upon dilution. Its predictions are confirmed by the second method which consists of an in vitro precipitation experiment. Thermal and visual evaluations are then obtained from an in vivo rabbit ear injection. Dexverapamil formulations that have low buffering capacity are shown to contribute to the incidence of phlebitis to a greater extent than the properly buffered formulations. The calculation and the in vitro precipitation experiment are found to be useful in formulating pH solubilized parenterals. They enable the formulator to optimize pH, drug concentration, and buffer concentration without the need for animal studies. The results of this study show the importance of selecting a buffer that provides adequate buffer capacity in the formulations.
Assuntos
Bloqueadores dos Canais de Cálcio/administração & dosagem , Flebite/induzido quimicamente , Verapamil/administração & dosagem , Verapamil/efeitos adversos , Animais , Precipitação Química , Feminino , Concentração de Íons de Hidrogênio , Masculino , Coelhos , EstereoisomerismoRESUMO
Formulation pH has been reported to be responsible for the incidence of phlebitis. In this study, the effect of pH on injection phlebitis is investigated. Buffers of varying pHs were examined for their ability to produce phlebitis in rabbits. Thermal measurements as well as visual evaluations were used for phlebitis quantitation. The results show that formulation pH between 3.0 and 11.0 does not contribute to the incidence of phlebitis when administered as an iv bolus injection.