高效液相色谱手性固定相法拆分联二萘酚、联二萘酚胺和联二萘胺对映体

在纤维素三(3,5-二甲基苯基氨基甲酸酯)(Ch iralcel OD-H)手性柱上对联二萘酚、联二萘酚胺和联二萘胺对映体的分离作了研究,分别考察了在流动相正己烷中,不同的醇类添加剂及醇类添加剂的浓度以及温度对手性分离的影响,当流动相为正己烷-正丁醇(90∶10,V/V),流速0.5 mL/m in,温度25℃时,联二萘酚、联二萘酚胺和联二萘胺对映体在Ch iralcel OD-H柱上的分离度Rs分别为2.27、2.40和9.28。研究了空间立体结构因素对手性分离的影响,在此基础上对其手性识别机理进行探讨。     

依托度酸及其中间体依托度酸甲酯的对映体分离研究

在自制的涂敷型纤维素三（3,5-二甲基苯基氨基甲酸酯）（CDMPC）和Pirlde型（S,S）-Whelk-O1两种手性柱上,对依托度酸及其中间体进行了对映体分离。考察了在流动相正己烷中,不同的醇类添加剂以及醇类添加剂的浓度对手性分离的影响,当流动相为正己烷-仲丁醇（0．39mol／L）,流速1．0mL／min,温度25℃时,对映体在CDMPC柱上分离效果好。研究了溶质的体积大小及空间立体结构因素对手性分离的影响。结果发现,对（S,S）-Whelk-O1柱,溶质与固定相之问以氢键为主的吸引作用是手性识别的主要因素,而对于CDMPC柱,溶质在手性空腔中的空间适应性很可能是手性识别的关键。     

纤维素键合手性固定相拆分6种萘满酮衍生物对映体

使用Chiralpak IC（纤维素-三（3,5-二氯苯基氨基甲酸酯）共价键合硅胶）手性柱,建立了采用手性固定相高效液相色谱拆分6种 α -芳基萘满酮类衍生物对映体的方法。考察了流动相中有机改性剂的种类和比例、柱温和流速对对映体分离的影响。结果显示6种化合物在异丙醇为改性剂的条件下均可获得较高的对映体分离度。热力学研究表明6种化合物对映体的手性拆分过程均受焓驱动影响,且低温有利于对映体分离。最终推荐分离化合物Ⅰ对映体的流动相是正己烷-异丙醇（90：10,v/v）;分离化合物Ⅱ、Ⅲ、Ⅳ对映体的流动相是正己烷-异丙醇（99：1,v/v）;分离化合物Ⅴ对映体的流动相是正己烷-异丙醇（85：15,v/v）;分离化合物Ⅵ对映体的流动相是正己烷-异丙醇（80：20,v/v）。柱温为25℃,流速为1.0 mL/min。6种化合物对映体均可在Chiralpak IC手性固定相上得到完全分离,证明该色谱柱对6种化合物具有较高的对映体选择性。     

手性固定相法分离芳香醇及芳酯对映体

在自制的涂敷型CDMPC和Pirkle型（S,S）-Whelk-O 1、（R,R）-DNB-DPEDA两类手性柱上,对1-苯乙醇、1-苯-1-丙醇及2-苯基丙酸甲酯进行了对映体分离。分别考察了在流动相正己烷中不同极性醇类添加剂、醇的浓度对这些溶质手性分离的影响,并研究了溶质的体积大小及立体结构因素对手性分离的影响,由此探讨了这两类手性柱对这些化合物手性识别的机理,发现在（S,S）-Whelk-O 1和（R,R）-DNB-DPEDA柱上溶质与固定相之间主要是吸引作用,而CDMPC手性识别的关键是溶质的体积大小、尤其是空间结构在手性空腔中的空间适应性,氢键作用对于CDMPC手性固定相的手性识别并不重要。     

高效液相色谱使用两种类型的纤维素-三(对甲基苯甲酸酯)固定相手性拆分非洛地平的比较

以高效液相色谱手性固定相法对非洛地平(FEL)进行手性拆分。分别采用两种类型的纤维素-三(对甲基苯甲酸酯)手性柱Chiralcel OJ-R和Chiralcel OJ-H进行比较实验,以正己烷-异丙醇(90:10, v/v)为流动相,考察了流动相、柱温对保留及手性拆分的影响。实验显示,两柱拆分FEL的van’t Hoff图均发生了转折,在高温区域为焓驱动,在低温区域为熵驱动。两柱在温度升高时拆分FEL的分离度均提高,其中OJ-H的分离度优于OJ-R。两种手性柱对FEL具有相似的拆分机理。     

顺式、反式氯氰菊酯和烯唑醇对映异构体的手性拆分

将纤维素-三(3，5-二甲基苯基氨基甲酸酯)(CDMPC)涂敷于氨丙基硅胶上制备成高效液相色谱(HPLC)手性固定相，对手性农药顺式、反式氯氰菊酯和烯唑醇对映异构体在正相条件下进行了手性拆分。分别以正己烷和石油醚为流动相，考察改性剂的含量；在正己烷流动相条件下考察了色谱柱长度、温度对拆分效果的影响。试验结果显示，改性剂含量的减少、长色谱柱及降低温度均有利于对映体的分离。该手性固定相对顺式、反式氯氰菊酯具有非常强的立体选择性，对烯唑醇也有较好的拆分能力。     

几种除草剂农药在高效液相色谱手性固定相上的对映体分离

采用正己烷-极性醇正相体系为色谱流动相,稳杀得、萘丙胺等几种不同种类的除草剂农药在Pirkle刷型(S,S)-Whelk-O1手性柱或自制的纤维素三(3,5-二甲苯基氨基甲酸酯)(CDMPC)手性柱上获得了成功的手性分离。研究了流动相中醇类改性剂对手性识别的影响,初步探讨了手性识别的机理,并摸索出最佳的对映体分离条件。     

高效液相色谱手性固定相法分离酸性化合物对映体

自制的涂敷型纤维素三(3,5-二甲基苯基氨基甲酸酯)(CDMPC)和Pirkle型(S,S)．Whelk-O1两种手性柱上,对6种酸性化合物(西替立嗪、外消旋萘普生、托品酸、布洛芬、酮洛芬以及2,2-二苯环丙烷羧酸)进行了对映体分离。考察了在流动相正己烷中,不同的醇类添加剂、酸性添加剂对手性分离的影响,研究了溶质的体积大小及空间立体结构因素对手性分离的影响,并初步探讨了手性识别机理。     

柱前衍生化-HPLC测定仲丁胺对映体的纯度

用3, 5-二硝基苯甲酸对仲丁胺进行柱前衍生, 将其衍生物在CHIRALCEL OD-H手性固定相上拆分, 并通过二极管阵列紫外检测器对其衍生物进行检测, 建立了一种拆分仲丁胺消旋体、测定仲丁胺光学纯度的新方法. 以正己烷和乙醇或异丙醇为流动相, 在CHIRALCEL OD-H手性固定相上对仲丁胺衍生物进行了拆分, 并考察了流动相组成和柱温对该对映体衍生物分离的影响, 获得较好的分析条件, 分离因子大于1.2. 非手性试剂柱前衍生化法测定仲丁胺光学纯度与旋光度方法比较, 结果一致. 方法可用于仲丁胺对映体的质量控制.     

农药甲霜灵对映体的高效液相色谱分离及手性拆分热力学研究

以正己烷 异丙醇为流动相 ,在纤维素 三 (3 ,5 二甲基苯基氨基甲酸酯 ) (CDMPC)涂敷型手性固定相上 ,对农药甲霜灵外消旋体进行了拆分 ,考察了流动相组成、柱温等对甲霜灵对映体的保留和分离的影响 ;对甲霜灵R、S对映体与固定相之间的保留和分离的热力学机理进行了讨论     

Surface‐imprinted microspheres prepared by a template‐oriented method for the chiral separation of amlodipine

The surface imprinting technique has been developed to overcome the mass‐transfer difficulty, but the utilization ratio of template molecules in the imprinting procedure still remains a challengeable task to be improved. In this work, specifically designed surface‐imprinted microspheres were prepared by a template‐oriented method for enantioseparation of amlodipine besylate. Submicron mesoporous silica microspheres were surface‐modified with double bonds, followed by polymerizing methacrylic acid to generate carboxyl modified mesoporous silica microspheres (PMAA@SiO₂). Afterwards, PMAA@SiO₂ was densely adsorbed with (S )‐amlodipine molecules to immobilize template molecules through multiple hydrogen bonding interactions. Then surface molecular imprinting was carried out by cross‐linking the carboxyl group of PMAA@SiO₂ with ethylene glycol diglycidyl ether. The surface‐imprinted microspheres showed fast binding kinetics of only 20 min for equilibrium adsorption, and the saturation adsorption capacity reached 137 mg/g. The imprinted materials displayed appreciable chiral separation ability when used as column chromatography for enantioseparation of amlodipine from amlodipine besylate, and the enantiomeric excess of (S )‐amlodipine reached 13.8% with only 2.3 cm column length by no extra chiral additives. Besides, the imprinted materials exhibited excellent reusability, and this allows the potential application for amplification production of amlodipine enantiomer.     

Rapid and efficient enantioseparation of (S)‐amlodipine by surface‐imprinted core–shell polymer microspheres

We present a protocol for the preparation of surface‐imprinted polymer microspheres by core–shell precipitation polymerization for the enantioseparation of (S)‐amlodipine. In this work, submicron mesoporous silica microspheres were prepared with gemini cationic surfactant as soft template. Molecularly imprinted polymers were coated on the silica supports with a low level of crosslinking, and the thickness of the thin‐walled imprinted shell was about 45 nm. The material showed fast binding kinetics for (S)‐amlodipine (within only 20 min for complete equilibrium), and the saturation adsorption capacity reached 309.2 mg/g, indicating the good accessibility of binding sites and improved mass transfer for target molecule. The imprinted microspheres exhibited an appreciable enantiomeric excess of (S)‐amlodipine of 11.3% when used as a glass chromatography column for the enantioseparation of (S)‐amlodipine from amlodipine besylate without extra chiral additives. The surface‐imprinted materials display potentially amplification for industrial enantioseparation of (S)‐amlodipine.     

Inclusion complexes of amlodipine besylate and cyclodextrins

In this paper the procedure for the preparation of inclusion complexes of amlodipine besylate with β-cyclodextrin (β-CD) and 2-hydrohypropyl-β-cyclodextrin (HPβ-CD) and their structural characterization was described. Molecular inclusion complexes of amlodipine besylate are prepared by the coprecipitation method and characterised by the application of spectroscopic methods FTIR, ¹H-NMR and XRD. The photosensitivity of amlodipine besylate in the inclusion complexes was also determined with respect to uncomplexed agent. DSC curves indicate the loss of the clear peak due to melting of amlodipine besylate at about 200°C, while on XR diffractograms certain reflections are lost belonging to amlodipine besylate in complexes. This indicates its inclusion in the vacancies of the host. The inclusion of amlodipine besylate with cyclodextrins increases the stability, i.e. decreases the photosensitivity of amlodipine besylate.      

Determination of amlodipine besylate by adsorptive square-wave anodic stripping voltammetry on glassy carbon electrode in tablets and biological fluids

The adsorptive and electrochemical behavior of amlodipine besylate on a glassy carbon electrode were explored in Britton-Robinson buffer solution by using cyclic and square-wave voltammetry. Cyclic voltammetric studies indicated the oxidation of amlodipine besylate at the electrode surface through a single two-electron irreversible step and fundamentally controlled by adsorption. The solution conditions and instrumental parameters were optimized for the determination of the authentic drug by adsorptive square-wave stripping voltammetry. Amlodipine besylate gave a sensitive adsorptive oxidation peak at 0.510 V (versus Ag/AgCl). The oxidation peak was used to determine amlodipine besylate in range 4.0×10⁻⁸ to 2.0×10⁻⁶ with a detection limit of 1.4×10⁻⁸ M. The procedure was successfully applied for the assay of amlodipine besylate in tablets (Norvasc)^®. The percentage recoveries were in agreement with those obtained by the reference method. Applicability to assay the drug in urine and serum samples was illustrated. The mean percentage recoveries were 96.31±1.18 and 96.98±1.17, respectively. The proposd method used for monotoring clinically relevant concntrations of drug in human urine and serum.     

Physico-chemical Characterization of Hydrated and Anhydrous Crystal Forms of Amlodipine Besylate

The antihypertensive drug substance amlodipine besylate crystallizes in two stable crystal forms, an anhydrate and a hitherto unknown monohydrate. Both forms have been characterized by thermal analysis, X-ray powder diffractometry, FTIR- and FT Raman spectroscopy. Moisture sorption- and desorption investigations reveal their unusual physical stability in a broad range of relative humidities. The monohydrate forms an isomorphic dehydrate upon dehydration, which was elucidated by variable temperature X-ray powder diffractometry. Physico-chemical properties as well as relative stabilities of the crystal forms are described and discussed based on a comprehensive analytical identification, and enable an estimation of practical relevance for manufacturing of amlodipine besylate solid dosage forms. This revised version was published online in August 2006 with corrections to the Cover Date.     

Synchronized separation of seven medications representing most commonly prescribed antihypertensive classes by using reversed‐phase liquid chromatography: Application for analysis in their combined formulations

A reversed‐phase high‐performance liquid chromatography method was developed for the simultaneous determination of the diuretic, hydrochlorothiazide, along with six drugs representing the most commonly prescribed antihypertensive pharmacological classes such as atenolol, a selective β₁ blocker, amlodipine besylate, a calcium channel blocker, moexipril hydrochloride, an angiotensin‐converting‐enzyme inhibitor, valsartan and candesartan cilexetil, which are angiotensin II receptor blockers, and aliskiren hemifumarate, a renin inhibitor, using irbesartan as an internal standard. The chromatographic separation was achieved using acetonitrile/sodium phosphate dibasic buffer (0.02 M, pH 5.5) at a flow rate of 1 mL/min in gradient elution mode at ambient temperature on a stationary phase composed of an Eclipse XDB‐C₁₈ (4.6 × 150 mm, 5 μm) column. UV detection was carried out at 220 nm. The method was validated according to ICH guidelines. Linearity, accuracy, and precision were satisfactory over the concentration ranges of 2–40 μg/mL for hydrochlorothiazide and candesartan cilexetil, 20–120, 10–160, 5–40, 20–250, and 5–50 μg/mL for atenolol, valsartan, moexipril hydrochloride, aliskiren hemifumarate, and amlodipine besylate, respectively. The method was successfully applied for the determination of each of the studied drugs in their combined formulations with hydrochlorothiazide. The developed method is suitable for the quality control and routine analysis of the cited drugs in their pharmaceutical dosage forms.     

Desirability function approach for the optimization of an in‐syringe ultrasound‐assisted emulsification‐microextraction method for the simultaneous determination of amlodipine and nifedipine in plasma samples

In the present study, an in‐syringe ultrasound‐assisted emulsification‐microextraction using a low‐density organic solvent was developed for simultaneous extraction and pre‐concentration of amlodipine besylate and nifedipine from plasma samples. The extracts were analyzed by high‐performance liquid chromatography with UV detection. Central composite design combined with desirability function was applied to find out the optimal experimental conditions providing the highest global extraction efficiency. The optimal conditions identified were volume of the extracting solvent 45 μL, ionic strength 18.95% w/v, sonication time 2.58 min, and centrifugation time 3 min. Under the optimal conditions, the proposed method was evaluated, and applied to the analysis of amlodipine besylate and nifedipine in plasma samples. The validation results of the method indicated a wide linear range (2–1200 ng/mL) with a good linearity (r² >0.9991) and low detection limits (0.17 ng/mL for amlodipine besylate and 0.15 ng/mL for nifedipine) with RSD less than 5.2% for both components, both in intra‐ and inter‐day precision studies. The applicability of the proposed in‐syringe ultrasound‐assisted emulsification‐microextraction coupled to high‐performance liquid chromatography with UV detection method was demonstrated by analyzing the drugs in spiked plasma samples.     

Simultaneous Enantioseparation and Rapid Determination of Atenolol and Amlodipine Besylate by Capillary Electrochromatography

Chromatographia - Simultaneous enantioseparation and rapid determination method of atenolol (AN) and amlodipine besylate (AMB) was firstly established using diphenylmethane...     

胃蛋白酶亲和有机聚合物毛细管整体柱的制备及性能考察

以热引发原位聚合方法制备了聚（甲基丙烯酸缩水甘油酯（glycidyl methacrylate,GMA）-乙二醇二甲基丙烯酸酯（ethyleneglycol dimethacrylate,EDMA））毛细管整体柱,对整体柱的性能进行了表征。结果表明,柱内部结构均匀、渗透性好;整体柱能够实现苯等中性小分子化合物的分离,具有反相色谱特征,重现性和稳定性良好。利用整体柱环氧基团的活性,采用间接法,以戊二醛为连接臂制备胃蛋白酶亲和手性整体柱。在毛细管电色谱模式下进行了柱分离性能研究,并对缓冲液pH值和运行电压等分离条件进行了考察。结果表明,亲和整体柱对4种碱性手性药物（奈福泮、氨氯地平、西酞普兰、扑尔敏）有拆分效果,奈福泮、氨氯地平、西酞普兰能达到基线分离。本文为蛋白质亲和毛细管电色谱整体柱的制备和应用提供了新的思路和方法。     

NP-HPLC分离氨氯地平对映体及其含量测定

建立直接拆分氨氯地平对映体的HPLC方法,并用于其含量测定.以CHIRALPAK AD-H为固定相,在正相条件下考察了流动相组成、流速、柱温等因素对氨氯地平对映体分离度的影响.在优化条件下,分别测定了氨氯地平对映体的含量.实验表明,以正己烷-乙醇-二乙胺(95 : 5 : 0.1,体积比)为流动相,流速 1.0 Ml/min,检测波长 360 nm,柱温 30 ℃,氨氯地平对映体的质量浓度均在0.01 ～0.06 g/L范围内线性关系良好(Rr=0.998 3,Rs=0.998 7).高、中、低3个浓度平均回收率(n=3)分别为99%、101%、101%,相对标准偏差依次为0.76%、0.68%、0.98%.该分析方法准确可靠、快速、简单、重复性好,可用于左旋氨氯地平工业化制备中动态拆分过程的跟踪分析及产品质量控制. 含量.实验表明,以正己烷-乙醇-二乙胺(95 : 5 : 0.1,体积比)为流动相,流速 1.0 Ml/min,检测波长 360 nm,柱温 30 ℃,氨氯地平对映体的质量浓度均在0.01 ～0.06 g/L范围内线性关系良好(r_R=0.998 3,r_S=0.998 7).高、中、低3个浓度平均 收率(n=3)分别为99%、101%、101%,相对标准偏差依次为0.76%、0.68%、0.98%.该分析方法准确可靠、快速、简单、重复性好,