Studies On Synthesis Process And Quality Standard For Xanthinol Nicotinate

The synthesis process of xanthinol nicotinate (XN) as a vasodilator was studied.Theophylline and nicotine were used as raw materials, cheap and low toxicityalcohol and 90% alcohol were choosed as reaction and purification solventrespectively. Orthogonal design was used to select the optimized synthetical processfor addition, condensation, neutralization and purification process as follows:Themole scale of theophyllin,epichlorohydrin, methylaminoethanol,sodium hydroxideand nicotine was 1∶1.12∶1.24∶1.03∶0.95. The reaction temperature was 15～20℃ and 78～80℃ , reaction time was 5h and 5.5h in the addition and condensationprocess. The scale of wet crude XN, 90% alcohol and active carbon was 1∶8∶0.03(g∶ml∶g), crystalized temperature was 10～15℃ and reflux time was 20 mins inthe purification process. The methods of IR and others were carried on in order toverify the structural formula of XN. The validation of analytical procedures wasconducted according to quality standard of XN in supplement of ChinesePharmacopoeia (ChP) in 2002. The results show that the structural formula of XN isright and XN can be analysed in accordance with the quality specification of ChP.The results of three lots repeat tests show that the optimal process for XN wasrepeated excellently and quality of products is stable and controllable. The yield ratewas 91.1%, which was close to the highest one of literatures. There were no "threewastes" to be discharged for the process. The process is suitable to industrializedproduction. A method of determination of XN and its related substances were studied byHPLC instead of UV and TLC in ChP. Mobile phase A and B weremethylalcohol-water of which scale is 12∶88 and 43∶57 respectively. (Five dropsof thriethylamine was added in the mobile phases, pH was adjusted to 3.1±0.1 using1mol/L H3PO4 solution). The detective wavelength was 267nm. The detection limitof XN and theophylline were 0.096μg/ml and 0.1034μg/ml respectively under thecondition. A method of determination of residual solvents in XN was established by GC.The chromatographic conditions were as follows:PEG-20M of 8% was spread on 101carrier;FID, The temperature of gasify room, column and detector were 120℃,90℃ and 240℃ respectively. Carried gas was N2. The detection limit of alcohol was25μg/ml.The results show that the two analytical methods were high precision, goodlinearity and specificity and suitable to daily use.