高效毛细管电泳法分离1-甲基-3-苯基丙胺对映体

提出了高效毛细管电泳拆分手性药物中间体1-甲基-3-苯基丙胺的方法。研究了缓冲溶液pH值、手性选择剂质量浓度、柱温、电压等因素对分离度的影响。在缓冲溶液浓度15mmol.L-1(NaH2PO4-Na2HPO4,pH7.6)、运行电压15kV、手性选择剂浓度为20g.L-1、毛细管温度18℃条件下,在4min内成功地分离了1-甲基-3-苯基丙胺对映体,其分离度为1.65。     

聚合-β-环糊精作手性选择剂的毛细管电泳法分离4种光学活性农药中间体

以聚合-β-环糊精作为毛细管区带电泳手性选择剂,成功分离了2-苯氧丙酸(PPA)、顺式-功夫菊酸(cis-PA)、1-苯基-2-(对甲苯基)乙胺(PTE)和1-苯基-2-(对甲氧基苯基)乙胺(PME)4种光学活性农药中间体的对映体。考察了不同手性选择剂及其浓度、背景电解质的pH等操作条件对分离的影响。结果表明,在12kV操作电压下、30mmol／Ltris-HCl背景电解质中,用14g／L聚合-β-CD作为手性选择剂,PPA和cis-PA对映体在pH6．0时,PIE和PME对映体分别在pH2．5和pH3．0时可以被较好分离。在优化的分离条件下,用聚合-β-CD作毛细管区带电泳手性选择剂分离PIE对映体的分离度为1．513,成功测定了两种旋光性PIE的对映体过量值。     

N-(2-甲基-6-乙基苯基)丙氨酸对映体的毛细管电泳分离

采用高效毛细管区带电泳法,以β-环糊精及其衍生物作为手性选择剂,对外消旋N-(2-甲基-6-乙基苯基)丙氨酸(EMPA)的两个对映体进行了手性分离,比较了环糊精种类、环糊精浓度、电解质溶液pH值、温度和电场强度对分离的影响.实验结果表明,采用2,6-O-二甲基-β-环糊精为手性选择试剂,环糊精浓度为40mmol/L、电解质溶液pH=5.5及温度为20℃时分离效果最佳,对映体基本达基线分离,线性范围为20～200mg/L,最低检测限为10mg/L.     

2-戊基-3-苯基-2,3-环氧丙醇对映体在手性柱上的拆分研究

采用多糖类手性固定相,建立2-戊基-3-苯基-2,3-环氧丙醇对映体的高效液相色谱(HPLC)手性分析方法。考察了手性柱类型、流动相组成、流速及柱温对2-戊基-3-苯基-2,3-环氧丙醇对映体拆分的影响。结果表明,以Chiralcel OD-H色谱柱(25×0.46cm,5μm)分离,采用正己烷-异丙醇(V/V,90∶10)作流动相,在流速为0.8 mL·min-1,柱温25℃,检测波长210nm的条件下,2-戊基-3-苯基-2,3-环氧丙醇对映体能达到基线分离,且具有较好的重复性和稳定性,可用于对映体的拆分及质量控制。该方法也适用于2-戊基-3-苯基-2,3-环氧丙醇类似物质的手性拆分。     

3-苯基乳酸的手性毛细管电泳拆分

考察了环糊精种类、环糊精浓度、缓冲溶液pH、分离电压、温度等因素对3-苯基乳酸手性分离的影响,并对分离条件进行了优化。结果表明,采用区带毛细管电泳技术,以0.03 mol/L的羟丙基-β-环糊精为手性选择剂,0.1 mol/L的磷酸缓冲溶液(pH 5.5)为电泳缓冲溶液,26 kV的分离电压,在25 ℃下可使3-苯基乳酸对映体达到基线分离,分离度为1.51。     

2-(9-蒽基)-2-羟基乙酸的毛细管电泳分离研究

以β-环糊精及其衍生物为手性选择试剂,采用高效毛细管电泳法对外消旋的2-(9-蒽基)-2-羟基乙酸进行了手性分离。研究了手性选择剂的种类、浓度,背景电解质的pH值等因素对对映体分离的影响。实验结果表明,采用55 g/L的磺化-β-环糊精为手性选择试剂,在pH 2.5的10 mmol/L三羟甲基氨基甲烷(Tris)-磷酸缓冲体系中,2-(9-蒽基)-2-羟基乙酸对映体可得到良好的分离。     

高磺化-β-环糊精毛细管电泳分离分析手性芳香仲醇

以高磺化-β-环糊精为毛细管电泳手性选择剂,建立了有效分离7种手性芳香仲醇对映体的方法.在20 mmol/L H3PO4-三乙醇胺为背景电解质(pH 2.5),6%(m/V) 高磺化-β-环糊精为手性选择剂(S-β-CD),柱温20 ℃,操作电压-15 kV,检测波长214 nm等优化条件下,所有芳香仲醇对映体均实现基线分离.以本方法测定了7种芳香酮不对称氢转移反应产物7种手性芳香仲醇的百分对映体过量值(% ee),其测定结果与高效液相色谱、气相色谱测定结果完全一致.本方法可以用于手性芳香仲醇光学纯度的测定.     

二元手性选择体系毛细管电泳/电化学分离检测手性药物酚苄明对映体

采用羟丙基-β-环糊精(HP-β-CD)和羟丙基甲基纤维素(HPMC)组成的二元手性选择剂体系,以8mmol/L三羟甲基氨基甲烷(Tris) 10mmol/L柠檬酸(Cit) 10mg/LHPMC 25mmol/LHP-β-CD为电泳运行液,在熔融石英毛细管(50μmi.d.×45cm)中,分离电压 15kV,方波安培检测,手性药物酚苄明对映体获得良好的基线分离,线性检测范围为4～105μmol/L,检出限为1.5μmol/L。对影响灵敏度和分离度的电泳运行液组成、手性选择剂(HP-β-CD、HPMC)浓度以及进样方式和样品介质等进行了详细讨论。应用于市售盐酸酚苄明片剂中酚苄明对映体的分离检测,取得满意结果。     

毛细管电泳法和高效液相色谱法拆分联萘二酚酸对映体

采用毛细管电泳法和高效液相色谱法直接拆分2,2′-二羟基-1,1′-联二萘-3,3′-二甲酸(HBNC)对映体.以四种不同的β-环糊精为手性添加剂,考察环糊精的种类与浓度、缓冲液pH值及浓度、分离电压、温度等因素对HBNC分离的影响.结果表明:采用10 mmol/L磺丁基醚-β-环糊精+20 mmol/L磷酸盐缓冲液(pH=7.0),20 kV分离电压,HBNC对映体在20 min内达到基线分离,分离度达到3.31.采用(S)-叔-亮氨酸基-(S)-1-(α-萘基)乙胺手性柱,正己烷-乙醇-三氟乙酸(97∶3∶0.2,V/V)流动相,HBNC对映体在40 min内也基本达到基线分离.     

高效液相色谱-手性流动相添加法拆分盐酸丙胺卡因对映体

以羧甲基-β-环糊精(CM-β-CD)为手性流动相添加剂,提出了拆分盐酸丙胺卡因对映体的高效液相色谱法。选用C18色谱柱,流动相为含0.4g·L-1的CM-β-CD的甲醇-乙腈-水(60+15+25)溶液,紫外检测波长为202nm,进样量为10μL,流量为0.4mL·min-1。结果表明:盐酸丙胺卡因对映体得到良好的分离,分离度为1.41。     

毛细管区带电泳对手性药物盐酸美西律和盐酸异博定的对映体分离

应用环糊精-毛细管区带电泳体系对手性药物盐酸美西律和盐酸异博定的对映体分离进行了研究。结果表明, 在所研究的手性选择剂α-环糊精, β-环糊精, 二甲基-β-环糊精, 羟丙基β-环糊精和γ-环糊精中, 羟丙基β-环糊精对所研究的手性药物分离效果较好。对盐酸美西律和盐酸异博定的最佳羟丙基-β-环糊精浓度分别为30mmol/L和9mmol/L, 最佳缓冲溶液浓度为100mmol/L Tris-H3PO4(pH2.3)。向缓冲溶液中加入0.05%羟丙基纤维素(HPLC)可改善分离。盐酸美西律获得了接近基线的手性分离, 而盐酸异博定亦获得了较好的分离。     

Complexation of triptolide and its succinate derivative with cyclodextrins: affinity capillary electrophoresis, isothermal titration calorimetry and 1H NMR studies

The complexation of the triptolide PG490 and its succinate derivative PG490-88Na with various cyclodextrins was studied using three complementary techniques: affinity capillary electrophoresis (ACE), isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR). The apparent binding constants of the complexes formed between the drugs and 8 CDs (α-CD, β-CD, γ-CD, HP-α-CD, HP-β-CD, HP-γ-CD, CM-β-CD and amino-β-CD) were determined by ACE through linear Scott's plots. The apparent and averaged binding constants of the complexes formed between PG490-88 and β-CD, γ-CD, HP-α-CD, HP-β-CD or HP-γ-CD are contained in the narrow range 135-167 M(-1). For the anionic CM-β-CD and cationic amino-β-CD, these constants are 38 and 278 M(-1), respectively, which is in accordance with electrostatic repulsions or attractions with the succinate moiety. ITC and NMR investigations for the binding constants determinations were performed for 2 CDs allowing high complexation: HP-β-CD and amino-β-CD. The three techniques provided similar results. ITC and NMR, in contrast to ACE, allowed to study the complexes formed between the neutral compound PG490 and neutral cyclodextrins. A more advanced characterization of the PG 490-88Na/amino-β-CD complex, which displays the highest apparent binding constant, was undertaken using NMR spectroscopy. The 1:1 stoichiometry of the complex was established by (1)H NMR 1D and selective 1D TOCSY experiments using the continuous variation method. Moreover, the 1D and 2D ROESY experiments revealed the inclusion of the isopropyl moiety of the triptolide derivative in the hydrophobic CD cavity. Altogether, the data provide strong evidences that the two triptolide compounds can be efficiently complexed with CD.     

毛细管电泳/非接触式电导法分离检测手性药物氨氯地平对映体

采用毛细管电泳/电容耦合非接触式电导( CE/C4 D),以18 mmol/L柠檬酸+6 mmol/L氨水+12 mg/L羟丙基甲基纤维素(HPMC)+ 35 mmol/L羟丙基-β-环糊精(HP-β-CD)为电泳运行液,熔融石英毛细管(50μm i.d.×45 cm,leff=40 cm),正高压(+15 kV)分离...     

毛细管电泳/非接触式电导法分离检测氧氟沙星对映体

采用毛细管电泳-电容耦合非接触式电导(CE-C4D),以20 mmol/L HAc + 6 mmol/L NaAc+12 mg/L羟丙基甲基纤维素(HPMC)+35 mmol/L羟丙基-β-环糊精(HP-β-CD)为电泳运行液,在熔融石英毛细管柱(45 cm×50 μm i.d.,有效长度 40 cm)中,正高压分离,手性药物氧氟沙星对映体获得良好的基线分离,线性检测范围为0.8～40 mg/L,检出限为0.3 mg/L.考察了电泳运行液组成、二元手性选择剂(HP-β-CD和HPMC)的浓度、进样方式和样品基质等对灵敏度和分离度的影响.本方法应用于市售外消旋和左旋氧氟沙星片剂中对映体的分离测定.     

Naproxen: Hydroxypropyl-β-Cyclodextrin:Polyvinylpyrrolidone Ternary Complex Formation

The aim of the present study was to investigate the effect of the presence of thewater-soluble polymer polyvinylpyrrolidone (PVP) MW = 24000 g/mol, on thecomplexation of the phototoxic anti-inflammatory drug naproxen, in its sodiumsalt form, with hydroxypropil-β-cyclodextrin (HP-β-CD). The datashown that the polymer interacts with the free naproxen and with thenaproxen:HP-β-CD inclusion complex. The presence of different proportions of PVP, in the 0–1%(w/w) rangesystematically increased the K_app of the naproxen:HP-β-CD inclusioncomplex formation. The cause of this increase is that the polymer interactswith the HP-β-CD with a binding constant of K₂ = 29000 ± 53 M^-1; and with the naproxen:HP-β-CD inclusion complex, to givea ternary complex naproxen:HP-β-CD:PVP. The binding constant of thisprocess was K₃ = 5350 ± 1 M^-1. NMR data revealed that in the ternary system, PVP is outside of the cyclodextrin, and therefore must be wholly or partially recovering the naproxen:HP-β-CD inclusion complex.     

反应萃取手性分离苯基琥珀酸对映体动力学研究

通过恒界面池研究了羟丙基-β-环糊精(HP-β-CD)萃取苯基琥珀酸对映体(PSA)动力学.采用伴随化学反应的萃取理论获得萃取动力学.实验分别考察了搅拌速率、界面面积、对映体浓度和萃取剂浓度等条件对PSA对映体萃取动力学的影响.实验结果表明:HP-β-CD萃取PSA对映体的反应为快反应;对对映体反应是一级反应,对萃取剂反应是二级反应;R-PSA,S-PSA反应速率常数分别为3.4×10-2m6mol-2s-1,9.96×103m6mol-2s-1.这些数据对萃取过程的设计是很重要的.     

Use of polystyrene nanoparticles to enhance enantiomeric separation of propranolol by capillary electrophoresis with Hp-beta-CD as chiral selector

We describe the use of polystyrene (PS) nanoparticles to manipulate chiral selectivity of propranolol analysis by capillary electrophoresis, by dispersing PS nanoparticles into the run buffer employing hydroxypropyl-β-cyclodextrin (HP-β-CD) as chiral selector. Distinct separational differences are observed between the buffer containing PS nanoparticles and buffer without, when changing separating conditions including PS nanoparticles concentration, pH, buffer concentration, HP-β-CD concentration and when adding an organic additive. Selectivity improvements are reflected by changes in the observed mobility as a result of interactions between the propranolol enantiomers and HP-β-CD governing the absorption process on the PS particles surface. The presence of PS nanoparticles increases the enantioseparation at low particle concentration in the presence of HP-β-CD as a chiral selector.     

Determining binding constants for 1:1 and 1:2 inclusion complexes of ester betulin derivatives with (2-hydroxypropyl)-β-cyclodextrin by affinity capillary electrophoresis

The complexation of ester betulin derivatives with (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) was studied by mobility shift affinity CE. Electrophoretic mobility for triangular peaks was calculated using the parameter a₁ of the Haarhoff–Van der Linde function instead of the peak top time. Dependences of the viscosity corrected electrophoretic mobility on HP-β-CD concentration were not described on the basis of only complexes with 1:1 stoichiometry due to the fact that these binding curves did not reach a plateau. However, the dependences were well described taking into account both 1:1 and 1:2 complexes. The presence of higher order equilibria was also revealed by x-reciprocal plots. The values of apparent binding constant logarithm, obtained for the first time, for 1:1 and 1:2 HP-β-CD complexes of betulin 3,28-diphthalate and betulin 3,28-disuccinate with 95% confidence interval limits in brackets are the same within error and are equal to 4.85 (4.73–4.95), 8.56 (7.75–8.82), 4.92 (4.86–4.97), and 8.54 (8.23–8.72) at 25°C, respectively. These values for 1:1 and 1:2 HP-β-CD complexes of betulin 3,28-disulfate at 25°C are 4.61 (4.57–4.64) and 7.11 (6.57–7.34), respectively. The binding constants for betulin 3,28-disulfate agree with the previously obtained results from the separation in the thermostatted capillary segment.     

固相萃取-毛细管电泳法测定兔血清中的山莨菪碱对映体

建立一种可用于定量的毛细管电泳法分离山莨菪碱对映体. 系统研究了三种手性选择剂: 羟丙基-β-环糊精 (HP-β-CD), 甲基-β-环糊精 (Me-β-CD), 羧甲基-β-环糊精(CM-β-CD) 及其浓度、缓冲溶液浓度和 pH 对山莨菪碱拆分的影响. 在110 mmol/L Tris-H3PO4缓冲液中加入20.0 mg/mL HP-β-CD和5.0 mg/mL CM-β-CD (pH 4.0)条件下, 山莨菪碱的4个对映体达到基线分离. 血清样品通过固相萃取预处理和浓缩, 对映体的固相萃取回收率在82.9%～90.7%, 相对标准偏差RSD%均小于7 %. 山莨菪碱的4个对映体血标准溶液浓度与电泳峰面积在77.86～0.39 μg/mL范围内呈良好的线性, r≥0.999, 检出限(S/N＝3)为0.08 μg/mL. 平均日间和日内精密度(RSD% )分别小于6.1% 和4.8%, 方法回收率为97.4% 和105.4%. 建立的方法准确、可靠, 应用于监测兔连续3 d口服75 mg 山莨菪碱后血清中山莨菪碱的血药浓度, 结果满意.     

Inclusion complexes of cyclodextrins with 4-amino-1,8-naphthalimides (part 2)

Fluorescence spectroscopy was used to characterize inclusion compounds between 4-amino-1,8-naphthalimides (ANI) derivatives and different cyclodextrins (CDs). The ANI derivatives employed were N-(12-aminododecyl)-4-amino-1,8-naphthalimide (mono-C₁₂ANI) and N,N′-(1,12-dodecanediyl)bis-4-amino-1,8-naphthalimide (bis-C₁₂ANI). The CDs used here were α-CD, β-CD, γ-CD, HP-α-CD, HP-β-CD and HP-γ-CD. The presence of CDs resulted in pronounced blue-shifts in the emission spectra of the ANI derivatives, with increases in emission intensity. This behavior was parallel to that observed for the dyes in apolar solvents, indicating that inclusion complexes were formed between the ANI and the CDs. Mono-C₁₂ANI formed inclusion complexes of 1:1 stoichiometry with all the CDs studied. Complexes with the larger CDs (HP-β-CD, HP-γ-CD and γ-CD) were formed by inclusion of the chromophoric ANI ring system, whereas the smaller CDs (α-CD, HP-α-CD and β-CD) formed complexes with mono-C₁₂ANI by inclusion of the dodecyl chain. Bis-C₁₂ANI formed inclusion complexes of 1:2 stoichiometry with HP-β-CD, HP-γ-CD and γ-CD, but did not form inclusion complexes with α-CD, HP-α-CD and β-CD. The data were treated in the case of the large CDs using a Benesi-Hildebrand like equation, giving the following equilibrium constants: mono-C₁₂ANI:HP-β-CD (K ₁₁ = 50 M^?1), mono-C₁₂ANI:HP-γ-CD (K ₁₁ = 180 M^?1), bis-C₁₂ANI:HP-β-CD (K ₁₂ = 146 M^?2), bis-C₁₂ANI:HP-γ-CD (K ₁₂ = 280 M^?2).