【作者】 刘红菊；

【导师】 蒋晔；

【作者基本信息】 河北医科大学 ， 药物分析学， 2005， 硕士

【摘要】 脂溶性药物极性小,不溶于水,有些甚至在甲醇中亦不溶或难溶,其分析方法一般采用正相高效液相色谱法和气相色谱法。但正相高效液相色谱法操作繁琐,成本高,影响因素多,不适于作为常规分析方法。气相色谱法则要求被测物质必须在工作温度下气化,因而不适于分析高沸点及热不稳定药物。非极性含氮有机化合物及其盐由于可在水中电离,其液相色谱测定方法多采用流动相中加入缓冲溶液,抑制其电离,有时还需加入少量扫尾剂(如三乙胺等)以防止药物的含氮基团与固定相残留硅醇基作用而使色谱峰拖尾,然而较高pH 的缓冲液对仪器和色谱柱均有损伤。本课题通过采用非水反相高效液相色谱法分离测定了几种非极性药物,探索了非极性药物在非水反相高效液相色谱法中的应用及保留规律,并首次采用非水反相高效液相色谱法分离测定了非极性含氮有机化合物及其盐类药物,研究结果表明非水反相高效液相色谱法的载样量大,分析时间短,非水体系可降低流动相的介电常数,减少了样品的电离,从而减少含氮基团与固定相残留硅醇基的作用,可改善峰形,提高柱效,并减少对色谱柱的损伤。因此,非水反相高效液相色谱法可做为脂溶性药物和非极性含氮有机化合物及其盐类药物的常规分析方法。更多还原

【Abstract】 The low-pole drugs, which are insoluble in water even inmethanol, were generally analyzed by normal phase highperformance liquid chromatography （NP-HPLC） and gaschromatography （GC）. Compared with RP-HPLC, NP-HPLC ismore tedious, too expensive and more easily influenced byexternal factors. So it is unsuitable for a regular analysis method.GC is generally used for the analysis of the sample that can bevolatilized at the work temperature. So GC can’t be used for theanalysis of the drugs with high boiling point or unstable at heat.And the retention time of low-pole drugs may be very long byRP-HPLC with the mobile phase involving water. Organicalkaline drugs were generally analyzed by RP-HPLC with themobile phase involving buffer solution and triethylamine, whichwould shorten the life of column. We analyzed retinol palmitate、ergocalciferol、colecalciferol、vitamin E acetate、phytonadione、aripiprazole、terbinafine hydrochloride、naftifine hydrochlorideby nonaqueous RP-HPLC, and studied the regularity of retention.The results show that nonaqueous RP-HPLC has many goodcharacteristics: the load capacity of column is larger; theretention time is shorter; nonaqueous organic solvent can cutdown the dielectric constant of mobile phase, increase theoryplate number; nonaqueous mobile phase can postpone the life ofcolumn. Therefore, nonaqueous RP-HPLC is suitable for analysisof fat-soluble drugs and organic alkaline drugs.PART 1 Nonaqueous RP-HPLC Determination of Fat-solubleVitamins1 Nonaquaous RP-HPLC Determination of Retinol Palmitate、Colecalciferol and Vitamin E Acetate SimultaneouslyObjective: To establish nonaqueous RP-HPLC to determineretinol palmitate 、colecalciferol and vitamin E acetate inmulti-vitamin injection simultaneously, and study the retentioncharacteristic.Method: The determination was performed on Warters C18column （150×4.6 mm, 5.0 μm） with the mobile phase ofacetonitrile-methanol-dichloromethane（70:20:10）,at a flow rateof 1.0 ml/min and the detection wavelength of 265 nm.Results: In the linear range the correlation coefficients wereall 0.999 9.The average recoveries were 99.1%, 100.6%, 99.2%,RSD was in the range of 0.32%⁰.70%.Conclusion: Nonaqueous RP-HPLC is suitable for theanalysis of fat-soluble vitamins in commercial form, with goodresolution, shorter time, wide linear range and high theory platenumber.2 Nonaqueous RP-HPLC Determination of Retinol Palmitate、Ergocalciferol 、Vitamin E Acetate and PhytonadioneSimultaneouslyObjective: To establish nonaqueous RP-HPLC to determineretinol palmitate 、ergocalciferol 、vitamin E acetate andphytonadione in multi-vitamin injection simultaneously, andstudy the retention characteristic.Method: The determination was performed on Warters C18column （150×4.6 mm, 5.0 μm） with the mobile phase consistingof acetonitrile-methanol （80:20）,at a flow rate of 1.0 ml/min andthe detection wavelenth of 265 nm.Results: In the linear range the correlation coefficients were all 0.9999.The average recoveries were 99.9%, 100.3%, 99.6%, 99.7% , RSD was in the range of 0.16%⁰.96%.Conclusion: Nonaqueous RP-HPLC is suitable for theanalysis of fat-soluble vitamins in preparation, with shorter time,wider linear range and high theory plate number.PART 2 Nonaqueous RP-HPLC Determination of Low-poleOrganic nitrogen Compounds and its Salts1 Nonaqueous RP-HPLC Determination of AripiprazoleObjective: To establish nonaqueous RP-HPLC to determinearipiprazole in material and tablet.Method: The determination was performed on DiamonsilC₁₈ column （250×4.6 mm, 5.0 μm） with the mobile phase ofmethanol-triethylamine （99.9: 0.1）,at a flow rate of 1.0 ml/minand the detection wavelength of 257 nm.Results: Aripiprazole was linear in the range of 1.57～405mg/L, r=0.9999.The recoveries of three levels were 100.1%、100.3%、99.8%, RSD <0.52%.Conclusion: The method is quick, with wide linear rangeand high theory plate number. There is not buffer solution andtriethylamine in mobile phase, so can postpone the life of column.So Nonaqueous RP-HPLC can be used for the quick analysis ofaripiprazole in material and tablet.2 Nonaqueous RP-HPLC Determination of TerbinafineHydrochloride and its Related SubstancesObjective: To establish nonaqueous RP-HPLC to determineterbinafine hydrochloride and its related substances in materialand cream.Method: The determination was performed on PhenomenexC₁₈ column （250×4.6 mm, 5.0 μm） with the mobile phase ofmethanol,at a flow rate of 1.0 ml/min and the detectionwavelength of 282 nm.Results: Terbinafine hydrochloride was linear in the rangeof 5.7×10-3¹.15 mg/ml, r=0.9999.The recoveries of three levelswere 99.5%、99.8%、100.2%, RSD <0. 86 %.Conclusion: The method is quick, with wide linear rangeand high theory plate number. The mobile phase is without buffersolution and triethylamine, so can decrease the damage tostationary phase. So Nonaqueous RP-HPLC is suitable for theanalysis of terbinafine hydrochloride and its related substances inmaterial and cream.3 Nonaqueous RP-HPLC Determination of NaftifineHydrochlorideObjective: To establish nonaqueous RP-HPLC to determinenaftifine hydrochloride.Method: The determination was performed on PhenomenexC18 column （250×4.6 mm, 5.0 μm） with the mobile phase ofmethanol,at a flow rate of 1.0 ml/min and the detectionwavelength of 254 nm.Results: Naftifine hydrochloride was linear in the range of4.12×10^-3 4.12×10^-2 mg/ml, r=0.9999.The average recoverywas 100.8%、100.2%、99.8%,RSD <0.52 %.Conclusion: The method is quick, with wide linear rangeand high theory plate number. The mobile phase is without buffer更多还原