Synthesis and physico chemical properties of 1-N-aminomethylated allopurinol derivatives

Fueron sintetizados y estudiados en sus respectivas solubilidad y lipofilicidad 1-N-aminometilderivados del Alopurinol (I), utilizando aminas alifáticas, alicíclicas y aromáticas, en búsqueda de derivados con mayor absorción por vía oral. Todos resultaron ser más solubles que (1) destacándose el 1-N-[4(ß-hidroxietil)-piperazinil] alopurinol, con una solubilidad molar de 21.6 x 10-2. La lipofilicidad de (1)en el sistema octanol/agua es de -0,62. Si bien todos los derivados resultaron ser más lipofílicos que (I), no se observa una clara relación entre punto de fusión, solubilidad y lipofilicidad, indicando que pueden estar involucrados factores estéricos de los sustituyentes1-N-aminomethylated Allopurinol derivatives were prepared using aliphatic, alicyclic and aromatic amines, in an attempt to improve aqueous solubility and oral absorption. Their physico chemical properties such as solubility and lipohilicity were determined. All of them have shown a greater solubility and lipohilicity in comparison with the parent drug [SM=0.5 x 10-2, Log P (oct/w=-0.62] but they were highly unstable to heat. The 1-N-[4(ß-hydroxyethyl) 1-piperazino methyl] allopurinol was the most soluble compound, SM=21.6 x l0-2. There was not a clear relationship between melting point, solubility) and lipohilicity indicating that steric factors might be involved.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Synthesis and physico chemical properties of 1-N-aminomethylated allopurinol derivatives

Fueron sintetizados y estudiados en sus respectivas solubilidad y lipofilicidad 1-N-aminometilderivados del Alopurinol (I), utilizando aminas alifáticas, alicíclicas y aromáticas, en búsqueda de derivados con mayor absorción por vía oral. Todos resultaron ser más solubles que (1) destacándose el 1-N-[4(ß-hidroxietil)-piperazinil] alopurinol, con una solubilidad molar de 21.6 x 10-2. La lipofilicidad de (1)en el sistema octanol/agua es de -0,62. Si bien todos los derivados resultaron ser más lipofílicos que (I), no se observa una clara relación entre punto de fusión, solubilidad y lipofilicidad, indicando que pueden estar involucrados factores estéricos de los sustituyentes1-N-aminomethylated Allopurinol derivatives were prepared using aliphatic, alicyclic and aromatic amines, in an attempt to improve aqueous solubility and oral absorption. Their physico chemical properties such as solubility and lipohilicity were determined. All of them have shown a greater solubility and lipohilicity in comparison with the parent drug [SM=0.5 x 10-2, Log P (oct/w=-0.62] but they were highly unstable to heat. The 1-N-[4(ß-hydroxyethyl) 1-piperazino methyl] allopurinol was the most soluble compound, SM=21.6 x l0-2. There was not a clear relationship between melting point, solubility) and lipohilicity indicating that steric factors might be involved.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Optimization of the Water-Insoluble Procedures for USP General Chapter Residual Solvents <467>

The water-insoluble procedures in US Pharmacopeia (USP) General Chapter Residual Solvents <467>, which are based on European Pharmacopoeia procedures, were optimized and modified before their inclusion in the chapter to improve their scope, performance, and ruggedness. The optimized procedures use a static headspace introduction system with a gas chromatograph equipped with a flame ionization detector. This article describes some of the key changes made to the USP published procedures, including use of dimethyl sulfoxide (DMSO) or dimethylformamide (DMF) as the solvent, addition of 5 mL of water and 1 mL of sample (dissolved in DMSO or DMF) to the headspace vial, use of a 3:1 GC split ratio, and use of new matrix-matched system suitability solutions. These procedures were verified with two different active pharmaceutical ingredients—hydroxyzine pamoate and prednisone. In the investigation, the more polar material (hydroxyzine pamoate) showed greater recoveries for the optimized procedures when prepared in DMSO. The less polar material (prednisone) typically had greater recoveries in DMF for the optimized procedures. During experimentation, insights into sample preparation, additional types of headspace instrumentation, solvent purity, and other parameters were also gained

HPLC Column Classification

ABSTRACT This Stimuli article represents the conclusions and recommendations of the USP Working Group on HPLC Columns. The working group included the five largest manufacturers of HPLC columns in the United States, along with the National Institute of Standards and Technology (NIST) and USP. This work attempts to facilitate the selection of HPLC columns by the analyst when performing a USP test