西司他丁中间体(+)-(S)-2,2-二甲基环丙羧酸的合成

目的:合成( )-(S)-2,2-二甲基环丙羧酸.方法:以2,2-二甲基环氧乙烷和三乙基膦醋酸酯为原料,经Witting环化生成三元环制备外消旋2,2-二甲基环丙羧酸,用L-(-)-薄荷醇为拆分试剂拆分得到光学活性目标化合物.结果:成功合成出( )-(S)-2,2-二甲基环丙羧酸,拆分收率提高到26.8%.结论:此方法操作简便,成本较低,收率较高,适于大量生产.     

制备S-(+)-2,2-二甲基环丙烷甲酸的研究进展

西司他丁与亚胺培南制成的复合剂泰能具有极强的广谱抗菌活性,是目前临床上治疗重症感染的首选药。西司他丁是肾脱氢二肽酶抑制剂,可以抑制亚胺培南在肾内的代谢,并增强其药效。S-(+)-2,2-二甲基环丙烷甲酸(酰胺)是合成西司他丁药物的关键手性中间体,目前有多种制备方法。本文主要从化学法和生物法两方面综述了通过不对称合成与拆分的方法制备S-(+)-2,2-二甲基环丙烷甲酸的研究进展,并对其制备方法进行了讨论和展望。     

(S)-(+)-2,2-二甲基环丙烷甲酰胺的合成

甘氨酸乙酯盐酸盐经重氮化反应制得重氮乙酸乙酯,与异丁烯在自制的手性催化剂—(R,R)-(+)-2,2′-亚异丙基双(4-叔丁基-2-噁唑啉)与三氟甲磺酸亚铜的络合物催化下进行不对称环丙烷化反应,制得(S)-2,2-二甲基环丙烷甲酸乙酯,碱性条件下水解,再与氯化亚砜反应得酰氯后氨解制得(S)-(+)-2,2-二甲基环丙烷甲酰胺,总收率约27%。     

1,3-二苯-1,3-丙二酮对N-甲基甲酰胺致小鼠急性肝损伤的保护作用

目的:考察1,3-二苯-1,3-丙二酮(DPPD)对N-甲基甲酰胺(NMF)急性肝损伤的保护作用。方法:小鼠经口分别灌胃给予DPPD 50,100,200 mg.kg-1,qd,连续4 d;腹腔注射给予致肝毒性剂量NMF 2 000mg.kg-1;染毒48 h后测定血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(as-partate aminotransferase,AST)、乳酸脱氢酶(lactate dehydrogenase,LDH)和总胆红素(total bilirubin,T-Bil)活性;留取肝脏组织,常规石蜡包埋切片,HE染色,光镜观察肝脏组织病理变化;制备肝匀浆,测定肝组织中还原性谷胱甘肽(GSH)、氧化性谷胱甘肽(GSSG)和丙二醛(malonaldehyde,MDA)含量,计算GSH/GSSG比值。结果:与对照组比较,模型组小鼠血清ALT,AST,LDH和T-Bil水平升高,肝组织GSH/GSSG比值及MDA含量升高,肝组织细胞变性坏死;预防性给予DPPD组ALT,AST和LDH水平明显降低,肝组织GSH/GSSG比值升高,MDA含量降低,肝脏病理损伤明显改善。结论:DPPD可有效抵御NMF对ICR小鼠肝脏的毒性损伤,调动机体抗氧化应激系统为可能的机制。     

手性拆分技术及其在手性药物合成中的应用新进展

手性拆分是获得手性药物的重要途径,该文对经典的结晶法拆分、动力学拆分和色谱分离法拆分等手性拆分方法的新进展进行综述,并介绍膜拆分法、萃取拆分法等新技术在手性药物合成中的应用。     

3-乙酰硫基-2-甲基丙酰基-L-脯氨酸的结晶体拆分工艺改进

目的　提高D - 3-乙酰硫基 - 2 -甲基丙酰基 -L -脯氨酸的质量和收率。方法　考察了不同结晶工艺水添加量,溶液pH值,温度及搅拌速度对D - 3-乙酰硫基 - 2 -甲基丙酰基 -L -脯氨酸收率和质量的影响。结果　新工艺在产品质量和收率方面均优于老工艺。结论　新工艺操作简便易行,稳定性好。     

手性聚酯复合膜的枸橼酸法制备及其在手性拆分中的应用

采用β-环糊精及其衍生物为手性选择剂,乙酸纤维素微滤膜为基质膜,枸橼酸为连接剂,经成酯反应制备了手性聚酯复合膜,并以D,L-色氨酸和D,L-扁桃酸为待拆分的手性分子,利用实验室自制的小型恒流膜过滤装置对手性聚酯复合膜的手性拆分性能进行研究,并考察p-环糊精的种类对手性复合膜手性拆分性能的影响.结果 表明,经p-环糊精修...     

3-环己烯-1-甲酸的手性拆分研究

目的 研究外消旋3-环己烯-1-甲酸的手性拆分,获得单一构型异构体.方法 通过化学拆分法中的生成非对映异构体拆分法来拆分外消旋3-环己烯-1-甲酸,以手性苯乙胺为手性拆分剂,外消旋3-环己烯-1-甲酸在丙酮中形成非对映体异构体并利用它们的溶解度差别来进行拆分.结果 拆分为(R)-(+)-3-环己烯-1-甲酸(收率28.3％)和(S)-(-)-3-环己烯-1-甲酸(收率28.7％),光学纯度均大于99％.结论 获得外消旋3-环己烯-1-甲酸的单一构型异构体.     

环丙贝特的合成

目的研究环丙贝特的合成工艺。方法以廉价苯乙烯为起始原料,依次经成环、Friedel-Crafts酰化、Baeyer-Villiger重排、醇解、Bargellini反应,成功合成了环丙贝特。结果本法总收率为56.2%,所得产物由1H-NMR确证结构。结论重排反应时避免直接使用危险性大的过氧酸,本合成工艺安全可行。同时,以丙酮和氯仿代替α-溴代异丁酸酯,显著降低生产成本。     

1-(α-萘甲基)-2甲基-6,7-二甲氧基-1,2,3,4-四氢异喹啉盐酸盐的HPLC手性拆分法及半制备

1-(α-Naphthylmethy)-2-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolinehydrochloride (code No, 86040)is a new kind of calcium antagonist. It has(+)and(一)enantiomers.Accordingly .the resolution and quantification of these two enantiomers have received agreat deal of attention,In this report the application of direct HPLC separation and semipreparation tothe determination of the enantiomeric composition of the new drug are described. All analysis andsemipreparation were performed with 25 cm×4. 6 mm i.d, 25 cm×8 mm i,d.and 30 cm×8 mmi.d. stainless steel column packed with a chiral β-cycledextrin bonded phase. Detection wavelengthwas 284 nm, The optimal composition of the mobile phase was EtOH─pH 4.0 phosphate buffer(35:65) at flow rate of 0. 3 ml·min^-1 for analysis and l.0 ml·min^-1 for semipreparation. Theseparation factor of the enantiomers was l.25. Purity of the semipreparation was 8l.4%,Quantityof semipreparation was 1 mg. This procedure was simple ,rapid and gave good resolution,The effectsof the composition of mobile phase, pH value, flow rate and column temperature on the resolution hadbeen sudied.     

A validated chiral HPLC method for the enantiomeric separation of tolterodine tartarate

An isocratic chiral HPLC method was developed for the separation of tolterodine tartarate enantiomers. The mobile phase consists of n-hexane and isopropyl alcohol in the ratio of 980:20 (v/v) with 1 ml diethylamine and 0.6 ml trifluoroacetic acid. Chiralcel OD-H (250 mm × 4.6 mm) column was used at constant room temperature. Flow rate was kept at 0.5 ml/min. This method is capable of detecting the S-isomer up to 0.1 μg/ml. The method was validated in terms of linearity, precision, limit of detection (LOD) and limit of quantification (LOQ).     

HPLC检测右旋佐匹克隆中的手性杂质

目的 建立检测右旋佐匹克隆中手性杂质的方法.方法 采用RP-HPLC法,Chiral-AGP色谱柱(150 mm×4.0 mm,5μm);流动相为20 mmol·L-1醋酸钠-醋酸缓冲液(Ph5);流速0.9 ml·min-1;检测波长225 nm;柱温30℃.结果 佐匹克隆对映体达基线分离,右旋佐匹克隆0～20.0 mg·L-1与峰面积线性关系良好(r=0.9998).结论 所建方法直接、简便、快速,可用于检测右旋佐匹克隆中手性杂质.     

二氢吡啶类钙离子拮抗药物手性分析及其立体选择性药动学研究进展

手性药物与安全有效用药的关系密切,大多数二氢吡啶类药物具有手性碳原子,以消旋体入药,进入体内后产生立体选择性处置特征,可能影响用药的安全有效。该研究围绕该类药物手性拆分及药动学特点,综述了近年来该类药物的手性高效液相色谱法(HPLC)和手性毛细管电泳法(CE)方法选择规律及体内分析应用;列举并比较了该类药物间的立体选择性药动学研究情况,发现该类药物部分具有明显的立体选择性差异,体内药效和毒性也随之不同。     

A comparison of matrix resolution method, ratio spectra derivative spectrophotometry and HPLC method for the determination of thiamine HCl and pyridoxine HCl in pharmaceutical preparation

A comparison of two spectrophotometric methods and a HPLC method were described in this work for the analysis of pyridoxine hydrochloride and thiamine hydrochloride in a vitamin combination. In the first method, A₁¹ (1%, 1 cm) values of these two compounds were calculated using absorbances measured at 246.8 and 290.5 nm in zero-order spectra. The matrix was written for A₁¹ (1%, l cm) values and the concentration of both compounds were determined using ‘Matlab’ software. In the second method, the measurements in the derivative of the ratio spectra were made at 297.8 and 309.5 nm for pyridoxine hydrochloride and at 245.6 and 257.7 nm for thiamine hydrochloride. The calibration graphs were established in the range 8–40 μg/ml of both vitamins. In the HPLC method, the separation of these compounds was realized on a Nucleosil 100-5 C₁₈ column with 0.1 M (NH₄)₂C0₃–water–methanol (5:15:80 v/v) as the mobile phase. Results of spectrophotometric and HPLC procedures were compared.     

A rapid HPLC method for plasma and serum mexiletine determination and its use in therapeutic drug monitoring

A HPLC method for the determination of mexiletine in human plasma and serum is described. Serum or plasma after addition of mexiletine and internal standard was extracted with diisopropyl ether. The extract was then evaporated and dissolved in the mobile phase. An aliquot of the solution was chromatographed on a reversed-phase C8 column. The peaks were detected by UV (214 nm) at room temperature. The limit of detection of mexiletine was approximately 0.02 mg/l of plasma or serum. The validity of the method is discussed and compared with other methods.     

手性高效液相色谱法拆分和测定缬沙坦对映体

目的建立测定缬沙坦对映体的高效液相色谱方法。方法采用L iChroCART Ch iraDex(250mm×4mm,5μm)手性柱,pH7.0磷酸盐缓冲液-甲醇(80∶20)为流动相,流速0.9mL/m in,柱温30℃,检测波长250nm。结果缬沙坦对映体在0.1~5μg/mL内呈良好的线性关系,检测限为0.02μg/mL,定量限为0.07μg/mL,平均加样回收率为98.8%。结论本方法简便、准确、灵敏,专属性强,适用于缬沙坦对映异构体的测定。     

高效液相色谱法测定去甲万古霉素血药浓度

目的：建立人血浆中去甲万古霉素反相高效液相色谱测定法,为临床监测血药浓度提供方法学基础。方法：采用液－液萃取法并选用２万古霉素为内标,以ＹＷＧ－ＲＰ１８色谱柱,流动相为乙腈－０．０５ｍｏｌ．Ｌ＾－１磷酸二氯（８：９２）,紫外２３６ｎｍ检测。结果：本法在０．８１～８１ｕｇ．ｍｌ＾－１间线性良好,相关系数ｒ＝０．９９９８（ｎ＝６）。日内日间精密度ＲＳＤ均小于３％,提取回收率均大于７５％。结论：本方法在     

Validated HPLC method for determination of amlodipine in human plasma and its application to pharmacokinetic studies

A rapid, simple and sensitive high-performance liquid chromatography (HPLC) method has been developed for quantification of amlodipine in plasma. The assay enables the measurement of amlodipine for therapeutic drug monitoring with a minimum detectable limit of 0.2 ng ml(-1). The method involves simple, one-step extraction procedure and analytical recovery was about 97%. The separation was performed on an analytical 125 x 4.6 mm i.d. Nucleosil C8 column. The wavelength was set at 239 nm. The mobile phase was a mixture of 0.01 M sodium dihydrogen phosphate buffer and acetonitrile (63:37, v/v) adjusted to pH 3.5 at a flow rate of 1.5 ml min(-1). The calibration curve was linear over the concentration range 0.5-16 ng ml(-1). The coefficients of variation for inter-day and intra-day assay were found to be less than 10%.     

反相高效液相色谱法测定人血浆中甲氨蝶呤的浓度

目的:建立反相高效液相色谱法测定人血浆中甲氨蝶呤浓度的方法. 方法:使用岛津LC-10AD高效液相色谱仪,Lichrosphere C18柱(5 μm,4.6 mm×250 mm),流动相为 0.025 mol·L-1 NaH2PO4溶液(pH5.5)-甲醇(72∶28),检测波长 313 nm,流速 1.0 mL·min-1, 柱温35℃,内标为阿魏酸.结果:甲氨蝶呤浓度在0.05～5.00 μg·mL-1范围内线性关系良好,回归方程为Y=3.094 2c 0.006 8(r=0.999 3),日内变异系数小于7%,日间变异系数小于10%;检测限为 20 ng·mL-1.结论:本法操作简便,适用于甲氨蝶呤的血药浓度测定及药代动力学研究.