Advancing ophthalmic delivery of flurbiprofen via synergistic chiral resolution and ion-pairing strategies

Flurbiprofen(FB),a nonsteroidal anti-inflammatory drug,is widely employed in treating ocular inflammation owing to its remarkable anti-inflammatory effects.However,the racemic nature of its commercially available formulation(Ocufen^(R))limits the full potential of its therapeutic activity,as the(S)-enantiomer is responsible for the desired antiinflammatory effects.Additionally,the limited corneal permeability of FB significantly restricts its bioavailability.In this study,we successfully separated the chiral isomers of FB to obtain the highly active(S)-FB.Subsequently,utilizing ion-pairing technology,we coupled(S)-FB with various counter-ions,such as sodium,diethylamine,trimethamine(TMA),and l-arginine,to enhance its ocular bioavailability.A comprehensive evaluation encompassed balanced solubility,octanol-water partition coefficient,corneal permeability,ocular pharmacokinetics,tissue distribution,and in vivo ocular anti-inflammatory activity of each chiral isomer salt.Among the various formulations,S-FBTMA exhibited superior water solubility(about 1–12 mg/ml),lipid solubility(1<lgP_(ow)<3)and corneal permeability.In comparison to Ocufen^(R),S-FBTMA demonstrated significantly higher in vivo antiinflammatory activity and lower ocular irritability(such as conjunctival congestion and tingling).The findings from this research highlight the potential of chiral separation and ion-pair enhanced permeation techniques in providing pharmaceutical enterprises focused on drug development with a valuable avenue for improving therapeutic outcomes.

RP/NP-HPLC法检测婴幼儿配方食品中维生素A和维生素E研究

优化婴幼儿配方食品中维生素A和维生素E含量检测的皂化-RPHPLC法和酶解-NPHPLC法,并对检验结果进行对比研究。结果表明:将婴幼儿配方食品样本复溶后再检测其中的维生素A和维生素E含量,提高了检测结果代表性,有利于批量化检测;乙酸乙酯-正己烷溶液(3∶2,v/v)为提取剂时,提取效果好且环保。维生素A和维生素E含量的检测结果分别在各自对应的浓度范围内呈良好线性关系,相关系数R2≥0.999,皂化-RPHPLC法中维生素A和维生素E定量限在27.3~142μg/100g之间,酶解-NPHPLC法中维生素A和维生素E定量限在10.8~112μg/100g之间,酶解-NPHPLC法灵敏度更高。在低中高三个添加水平下,维生素A加标回收率在82.2%~96.8%之间,RSD在1.0%~4.6%之间;维生素E加标回收率在83.5%~100.6%之间,RSD在1.9%~9.7%之间。皂化-RPHPLC法和酶解-NPHPLC法检验结果无显著性差异。优化后的检测方法简单高效,样品代表性好。

RPHPLC法同时测多索茶碱和3种抗癫痫药血药浓度

目的建立能够同时测多索茶碱、苯妥英钠、卡马西平和苯巴比妥这4种药血药浓度的反相高效液相色谱法。方法采用日本岛津LC-20AT高效液相色谱仪,以ODS-C18柱(150 mm×4.6 mm×5μm)为色谱柱,流动相为甲醇-水(50:50),流速为0.8 mL/min,柱温为20℃,检测波长210 nm,进样量20μL。结果多索茶碱、苯妥英钠、苯巴比妥和卡马西平线性关系良好,线性范围分别为2.5～30.0μg/mL(r=0.999 5),2.5～30.0μg/mL(r=0.999 4),2.5～50.0μg/mL(r=0.999 7),1.0～20.0μg/mL(r=0.999 7),方法回收率均>95%,日间的精密度和日内的精密度均<6%(n=5)。结论该方法迅速、准确、灵敏,4种药物能够被良好分离,且没有出现被测药物之间相互干扰,可用于临床监测血药浓度。

IP-RPHPLC法检测电针后肥胖大鼠肝脏组织中ATP、ADP和AMP含量

目的建立一种离子对反相高效液相色谱（IP-RPHPLC）法并将其用于检测电针对肥胖大鼠肝脏组织中ATP、ADP和AMP含量的影响。方法应用岛津SIL-20AT高效液相色谱系统,Megres-C18（5μm,250mm×4.6mm）耐水性色谱柱,对大鼠肝脏组织中ATP、ADP和AMP进行分离,流动相为0.18mol/L的磷酸二氢钾缓冲液（含5%甲醇且pH=6.25）,检测波长为254nm,流速为0.8mL/min,进样体积为20μL,柱温为25℃。结果 ATP在1.1~212.2μg/mL（r=0.999 9）,ADP在0.9~180.0μg/mL（r=0.999 9）及AMP在0.9~181.8μg/mL（r=0.999 7）范围内线性关系良好。ATP、ADP和AMP平均回收率分别为96.4%、98.3%、100.8%;RSD分别为2.50%、2.88%、4.14%;日内和日间精密度RSD分别为0.06%~0.40%和0.06%~0.69%;准确度均在99.0%~108.6%之间;ATP、ADP和AMP检测限为0.11、0.09、0.045μg/mL。结论建立的高效液相色谱法用于检测大鼠肝脏组织中ATP、ADP和AMP含量简便、快速并且准确可靠,为针刺干预治疗后组织中小分子生物活性物质浓度的检测等研究工作奠定了基础。

RPHPLC法测定人血浆中二甲双胍浓度

目的:建立测定人血浆中二甲双胍浓度的反相高效液相色谱法。方法:人血浆标本以盐酸阿替洛尔为内标,酸化后以乙腈沉淀蛋白、二氯甲烷反洗上清液后,取上清液进行色谱分析,以5 mmol/L SDS∶0.04 mol/L KH2PO4∶CH3OH=1∶1∶1.7为流动相,流速1 ml/min,经Agilent Zorbax SB C18(150×4.6 mm,5μm)柱分离,检测波长240 nm。结果:二甲双胍标准曲线范围10～5 000μg/L,y=0.001 12x+0.012 671(r=0.999 4),最低检测限为10μg/L,高、中、低3种浓度的日内精密度均<7%,日间精密度均<8%,萃取回收率75.6%～86.6%。结论:该方法简便、快速、准确,可用于人体内二甲双胍药动学研究和临床血药浓度监测。

反相高效液相色谱法(RPHPLC)测定水体中硝酸盐及亚硝酸盐

文章提出了一个快速RPHPLC同时测定水体中NO_3^-和NO_2^-的新方法。使用UV210检测,磷酸为流动相,最低检出量(S/N=2):NO_3^-为0.08ng,NO_2^-为0.6ng。文章对流动相的pH及浓度进行了优化并对某地自来水及城市排放水进行了测定。全部分析时间仅为3min。

Ion-Pair Photodissociation of Trichloromonofluoromethane

fragments, F- and Cl- including two isotope species 35Cl- and 37Cl-, are observed in the photoexcitations of CFC13. The ion-pair anion efficiency spectra of 35Cl- and 37Cl- are recorded in the photon energy range of 7.75-22.00 eV. The threshold of ion-pair dissociation CFCl3-CFC12＋＋Cl- is experimentally determined to be 7.944-0.04 eV. With the references of the high-resolution photoabsorption spectra reported in the literatures, we make tentative assignments of the electron valence-to-Rydberg transitions. Furthermore, the multibody ion-pair fragmentation processes to Cl- are discussed by comparison between the calculated thermochemical thresholds and the experimental efficiency spectrum.

Ion-pairing HPLC methods to determine EDTA and DTPA in small molecule and biological pharmaceutical formulations

Ion-pairing high-performance liquid chromatography-ultraviolet （HPLC-UV） methods were developed to determine two commonly used chelating agents, ethylenediaminetetraacetic acid （EDTA） in Abilify （a small molecule drug with aripiprazole as the active pharmaceutical ingredient） oral solution and die- thylenetriaminepentaacetic acid （DTPA） in Yervoy （a monoclonal antibody drug with ipilimumab as the active pharmaceutical ingredient） intravenous formulation. Since the analytes, EDTA and DTPA, do not contain chromophores, transition metal ions （Cu2＋, Fe3＋） which generate highly stable metallocom- plexes with the chelating agents were added into the sample preparation to enhance UV detection. The use of metallocomplexes with ion-pairing chromatography provides the ability to achieve the desired sensitivity and selectivity in the development of the method. Specifically, the sample preparation in- volving metallocomplex formation allowed sensitive UV detection. Copper was utilized for the de- termination of EDTA and iron was utilized for the determination of DTPA. In the case of EDTA, a gradient mobile phase separated the components of the formulation from the analyte. In the method for DTPA, the active drug substance, ipilimumab, was eluted in the void. In addition, the optimization of the concentration of the ion-pairing reagent was discussed as a means of enhancing the retention of the aminopolycarboxylic acids （APCAs） including EDTA and DTPA and the specificity of the method. The analytical method development was designed based on the chromatographic properties of the analytes, the nature of the sample matrix and the intended purpose of the method. Validation data were presented for the two methods. Finally, both methods were successfully utilized in determining the fate of the chelates.

A Method for Detection of Trace Concentrations of Underivatized Amino Acid in Hydrothermal Fluids by Ion-Pairing Reversed-Phase UPLC-ESI-QTOF-MS

Investigation of amino acids in hydrothermal systems is of prime importance for the understanding of geochemistry and microbiology of hydrothermal vents and plumes, for carbon and metals global cycles, for metabolism of some hydrothermal microorganisms and for the origin of life issue. Extensive theoretical and experimental work on amino acids behaviour in hydrothermal fluids has been done, conversely only few data exist on natural samples. Because each hydrothermal vent is unique, the more data we collect the better we will be able to address each of these questions. Usually amino acids in hydrothermal fluids have been measured by HPLC-FLD. The chromatographic separation was at least 26 min and up to 135 min and the required derivatization step may be time consuming, may use harmful chemicals and may be source of contamination. Alternatively, we describe here a method combining quickness (4.5 min), high resolution (10,000), very low LOD (sub-ppb) and without derivatization. Characterisation and separation of 10 relevant proteinogenic underivatized amino acids was achieved by ion-pairing reversed-phase Ultra-high Performance Liquid Chromatography-Electrospray Ionisation-Quadrupole Time of Flight-Mass Spectrometry (UPLC-ESI-QTOF-MS). Excellent linearity in the response was obtained for all amino acids with correlation coefficients > 0.9921. This method was successfully applied to natural hydrothermal fluid samples from ultramafic-hosted vents of the Mid-Atlantic Ridge region. Results are consistent with the only 2 other studies published on ultramafic-hosted vents and complete the few available data.

Synthesis and Crystal Structure of a Novel Ion-pair Compound Consisting of 1-(4-Bromobenzyl)pyridinium Cation and 7,7,8,8-Tetracyanoquinodimethanide Anion

The title compound [BrBzPy][TCNQ] （BrBzPy^＋=1-（4-bromobenzyl）pyridinium cation, TCNQ = 7,7,8,8-tetracyanoquinodimethanide anion） was synthesized by the reaction of [BrBzPy]Br and LiTCNQ in ethanol solution and its structure was determined by single-crystal X-ray diffraction. The crystal belongs to monoclinic, space group P21/c with a = 14.067（3）, b = 7.3089（14）, c = 23.796（4）A, β = 122.011（9）°, V= 2074.6（7）A^3, Z = 4, C24H15BrN5, Mr = 453.32, Dc = 1.451 g/cm^3,μ = 2.002 mm^-1, S = 1.047, F（000） = 916, R = 0.0398 and wR = 0.0921. The most prominent structural features are the completely segregated stacking columns of the TCNQ- anions and [BrBzPy]^＋ cations. In a TCNQ column, the centroid-to-centroid distances of the neighboring anions of TCNQ are 3.2693 and 4.9464 A, respectively.

The Quantum Scattering Study for Ion-pair Formation Reaction Na+I_2→Na^+I_2^- with the LCAC-SW method

The selected-state probabilities of collinear ion-pair formation process Na+I2→Na++I2-on Aten-Laming-Los two-State potential energy surface have been calculated by using LCAC-SW method. The results show that reaction probabilities are oscillatory with collision energy; the threshold energy of this ioniZation reaction is 2.8 ev, which is in modest agreement with experimental result.

Synthesis and Crystal Structure of a Novel Ion-pair Compound Consisting of 1,3-Bis(4-cynobenzyl) Imidazole Cation and 7,7,8,8-Tetracyanoquinodimethanide Anion

A novel compound [（CNBz）2Im]2（TCNQ）3（CH3CN）（（CNBz）2Im = 1,3-bis（4-cyano-benzyl） imidazole cation,TCNQ-1 = 7,7,8,8-tetracyanoquinodimethanide anion） was synthesized by the reaction of [（CNBz）2Im]Br and LiTCNQ in water and its structure was determined by single-crystal X-ray diffraction.The crystal belongs to monoclinic,space group P21/c with a = 10.1823（17）,b = 20.292（3）,c = 16.952（3） ,β = 104.73（0）°,V = 3387.6（10）3,Z = 4,C39H24N11,Mr = 646.69,Dc = 1.268 g/cm3,μ = 0.080 mm-1 and F（000） = 1340.The structure was solved by direct methods and refined to R = 0.0596 and wR = 0.0911 for 2690 observed reflections（Ⅰ 〉 2σ（Ⅰ））.The most prominent structural feature is that there are two types of TCNQ entries（TCNQ-1 and TCNQ0） in agreement with the IR spectra analysis of the compound.

Ion-pair induced solvent extraction of lithium(Ⅰ)from acidic chloride solutions with tributyl phosphate

Lithium(Li)is an important energy metal in the 21st century.However,the selective recovery of Li is still a big challenge,especially from acidic solutions with multiple metal ions existence.Herein we report a new ion pair induced mechanism for selectively extracting Li^(+)from acidic chloride solutions by tributyl phosphate(TBP).It is shown that the acidity and the chloride ions in the aqueous phase have great effects on the extraction of Li^(+).The FT-IR,UV-Vis and ESI-MS experiments provide solid evidence for the formation of ion-pair complex[Li(TBP)_n(H_(2)O)_(m)]^(+)[FeCl_(4)]^(-)(n-1,2,3;m-0,1)in the organic phase,which brings about the effective and efficient extraction of Li^(+).This mechanism can overcome the Hofmeister bias and allow for the selective extraction of Li^(+) from the extremely hydrophilic chlorides.It has also been proved that the loaded Li in TBP can be effectively stripped by concentrated HCl solution with a Li/Fe separation factor>500.The understanding of the ion-pair transport mechanism is helpful for optimizing the recovery process or further advancing more efficient recovery techniques for Li from acidic liquor.

Synthesis and Crystal Structure of an Ion-pair Compound: [H_2(teta)]^(2+)·[Ni(CN)_4]^(2-)·2H_2O (teta = Meso-5,7,7,12,14,14-hexamethyl- 1,4,8,11-tetraazacyclotetradecane)

The ion-pair compound [H2（teta）]^2＋·[Ni（CN）4]^2-·2H2O （C20H42N8NiO2, teta = meso- 5,7,7,12,14,14-hexamethyl- 1,4,8,11-tetraazacyclotetradecane） was synthesized and characterized by single-crystal X-ray diffraction. The crystal belongs to monoclinic, space group P211n with a = 10.0784（10）, b = 9.5411（7）, c = 14.1010（14）А, β= 106.752（2）°, V= 1298.4（2）A^3, Mr = 485.33, Z= 2, De= 1.241 g/cm^3,μ（MoKα） = 0.778 mm^-1 and F（000） = 524. The structure was refined to R = 0.0391 and wR = 0.0870 for 2614 observed reflections with I 〉 2σ（I）. The title compound contains one [Ni（CN）4]^2- anion, one protonated macrocyclic tetraamine cation [H2（teta）]^2＋ and two water molecules. There are multiform hydrogen bonds in the compound to link the different components and stabilize the crystal structure.

Novel additives for the separation of organic acids by ion-pair chromatography

This paper proposes the use of novel surfactant additives for the separation of organic acids by ion-pair chromatography and studies the influences of surfactants on the chromatographic separation behaviors.Researches have been carried out on both silica gel matrix and polymer supporters in order to compare the two ordinary kinds of stationary phases,and the phenomenon is similar. Separation is based on differences in the stabilities of analyte-additive complexes in solution.Retention times of analytes can ...

Preparation,Crystal Structure and Density Functional Theory Calculations of the Ion-pair Compound [Cl2Bz(3-MeQl)](TCNQ)

A novel compound [Cl2Bz（3-MeQl） ]（TCNQ） （[Cl2Bz（3-MeQl） ]^＋ = 1-（3,4-dichlo-robenzyl） 3-methlquinoline cation,TCNQ-= 7,7,8,8-tetracyanoquinodimethanide anion） has been synthesized by the reaction of [Cl2Bz（3-MeQl） ]Br and LiTCNQ,and its structure was determined by single-crystal X-ray diffraction. The crystal belongs to monoclinic,space group P21/c. The structure analysis shows that the anions are stacked into a column with isolated π-dimers,and there is one type of TCNQ entries（TCNQ^-） ,in agreement with the IR spectra analysis and density functional theory calculations of the compound. The most prominent structural features are the completely segregated stacking columns of the TCNQ- anions and [Cl2Bz（3-MeQl）]＋ cations.

Enantiomeric Separation of Amino Alcohols by Ion-pair Chromatography

Enantiomers of four amino alcohols were resolved by ion-pair chromatography with (+)-10-camphorsulphonic acid as chiral counter ion. Studies of the influence of the mobile phase composition, the solute structure and the mobile phase flow-rate on separation are presented. Under the optimized conditions enantiomeric propanolol, norephedrine, metropolol and salbutamol were separated using dichloromethane-1-pentanol (97:3 v/v) as mobile phase on Lichrospher-100-DIOL column.

Theoretical Study on the Ion-pair Formation Mechanism for the Li+I_2 →Li^+ + I_2^- System

For the Li + I2 →Li+ + I2- system, theoretical study has been performed on the QCISD(T) level by using the ab initio method. The collision complex in ion-pair formation process was found and optimized. These results show that the crossed molecule beam (CMB) experimental phenomenon is verified and the detailed geometry is given for the first time. A mechanism for ion-pair formation was proposed in detail. The position where the collision complex occurs affects the reaction path. Specifically, the process has threshold when the collision complex appeared before the crossing point between the covalent and ionic state potential energy surfaces. On the contrary, the process has no threshold after the crossing point. Theoretically, the title system belongs to the former case.

Ion-Pair Dissociations of Br CN by Electron Impacts

Ion-pair dissociation is an important molecular process and frequently happens when the target molecule is pumped to its electronically superexcited states. In contrast to the experimental studies of photoexcitation ion-pair dissociation, there are some experimental challenges in the electron-impact ion-pair dissociation study, in particular, on determination of the energetic threshold. Here we report an experimental development for the ion-pair dissociation study by using the monochromized electron impacts. As an example, the threshold of BrCN→Br^-+CN^+ is determined as 13.78 eV according to the appearance energy of CN^+ signals, meanwhile, the time-sliced ion velocity image of CN^+ is recorded at 16.09 eV and indicates an anisotropic distribution of the CN^+ momentum.

Synthesis and Structure of a Novel Ion-pair Palladium(Ⅱ) Compound Containing 2-Thioxo-1,3-dithiole-4,5-bis(thiolate)

A novel ion-pair palladium（Ⅱ） compound, （NOzBzPy）2[Pd（dmit）2] （NO2BzPy^＋ = 1-（4-nitrobenzyl）pyridinium, dmit^2- = 2-thioxo-1,3-dithiole-4,5-bis（thiolate））, was synthesized and characterized by single-crystal X-ray structure determination. This compound crystallizes in the monoclinic system, space group P21/n with a = 10.4463（11）, b = 8.5627（9）, e = 20.017（2）A, β = 97.7730（10）°, V = 1774.1（3）A^3, Z = 2, C30H22N4O4S10Pd, Mr = 929.52, Dc = 1.740 g/cm^3,μ = 1.155 mm^-1, S = 1.006, F（000） = 936, R = 0.0354 and wR = 0.0675. The most intriguing general structural feature of the compound is the completely segregated columnar stacks of anions and cations. There exist hydrogen-bonding interactions within the cation column.