Simple in‐house flow‐injection capillary electrophoresis with capacitively coupled contactless conductivity method for the determination of colistin

An in‐house flow‐injection capillary electrophoresis with capacitively coupled contactless conductivity detection method was developed for the direct measurement of colistin in pharmaceutical samples. The flow injection and capillary electrophoresis systems are connected by an acrylic interface. Capillary electrophoresis separation is achieved within 2 min using a background electrolyte solution of 5 mM 2‐morpholinoethanesulfonic acid and 5 mM histidine (pH 6). The flow‐injection section allows for convenient filling of the capillary and sample introduction without the use of a pressure/vacuum manifold. Capacitively coupled contactless conductivity detection is employed since colistin has no chromophore but is cationic at pH 6. Calibration curve is linear from 20 to 150 mg/L, with a correlation coefficient (r²) of 0.997. The limit of quantitation is 20 mg/L. The developed method provides precision, simplicity, and short analysis time.     

Simultaneous determination of caffeine,paracetamol, and ibuprofen in pharmaceutical formulations by high‐performance liquid chromatography with UV detection and by capillary electrophoresis with conductivity detection

Paracetamol, caffeine and ibuprofen are found in over‐the‐counter pharmaceutical formulations. In this work, we propose two new methods for simultaneous determination of paracetamol, caffeine and ibuprofen in pharmaceutical formulations. One method is based on high‐performance liquid chromatography with diode‐array detection and the other on capillary electrophoresis with capacitively coupled contactless conductivity detection. The separation by high‐performance liquid chromatography with diode‐array detection was achieved on a C₁₈ column (250×4.6 mm², 5 μm) with a gradient mobile phase comprising 20–100% acetonitrile in 40 mmol L^?1 phosphate buffer pH 7.0. The separation by capillary electrophoresis with capacitively coupled contactless conductivity detection was achieved on a fused‐silica capillary (40 cm length, 50 μm i.d.) using 10 mmol L^?1 3,4‐dimethoxycinnamate and 10 mmol L^?1 β‐alanine with pH adjustment to 10.4 with lithium hydroxide as background electrolyte. The determination of all three pharmaceuticals was carried out in 9.6 min by liquid chromatography and in 2.2 min by capillary electrophoresis. Detection limits for caffeine, paracetamol and ibuprofen were 4.4, 0.7, and 3.4 μmol L^?1 by liquid chromatography and 39, 32, and 49 μmol L^?1 by capillary electrophoresis, respectively. Recovery values for spiked samples were between 92–107% for both proposed methods.     

Determination of pharmaceuticals classified as emerging pollutants using capillary electrophoresis with capacitively coupled contactless conductivity detection

A study on the simultaneous separation of 13 pharmaceutical products by capillary electrophoresis with capacitively coupled contactless conductivity detection was presented. The parameters of the background electrolyte, such as pH, organic additives as well as types and concentrations of cyclodextrins (CD) were studied. The optimal separation conditions were achieved with a background electrolyte consisting of 9 mM Tris/5 mM lactic acid at pH 8.0, containing 5% n-propanol, 0.025% gamma-CD, 0.075% hydroxyl-beta-CD and 0.15% dimethyl-beta-CD. Limits of detections ranged from 61 to 1676 microg/L (S/N=3) and the relative standard deviations for migration time and peak area were below 2 and 6%, respectively. This demonstrated the potential of the capillary electrophoresis-capacitively coupled contactless conductivity detection method for biomedical and environmental analysis, as shown in the determination of pharmaceuticals identified as emerging pollutants in water samples.     

Simultaneous determination of atenolol and amiloride in pharmaceutical preparations by capillary zone electrophoresis with capacitively coupled contactless conductivity detection

Capillary zone electrophoresis coupled with a capacitively coupled contactless conductivity detector (CE‐C⁴D) has been employed for the determination of atenolol and amiloride in pharmaceutical formulations. Acetic acid (150 mm ) was used as background electrolyte. The influence of several factors (detector excitation voltage and frequency, buffer concentration, applied voltage, capillary temperature and injection time) was studied. Non‐UV‐absorbing L‐valine was used as internal standard; the analytes were all separated in less than 7 min. The separation was carried out in normal polarity mode at 28°C, 25 kV and using hydrodynamic injection (25 s). The separation was effected in an uncoated fused‐silica capillary (75 μm, i.d. × 52 cm). The CE‐C⁴D method was validated with respect to linearity, limit of detection and quantification, accuracy, precision and selectivity. Calibration curves were linear over the range 5–250 μg/mL for the studied analytes. The relative standard deviations of intra‐ and inter‐day migration times and corrected peak areas were less than 6.0%. The method showed good precision and accuracy and was successfully applied to the simultaneous determination of atenolol and amiloride in different pharmaceutical tablet formulations. Copyright © 2010 John Wiley & Sons, Ltd.     

微芯片毛细管电泳快速测定盐酸洛美沙星

采用微芯片毛细管电泳非接触电导检测法快速测定了盐酸洛美沙星胶囊中盐酸洛美沙星的含量。探讨了缓冲液类型、浓度,添加剂种类、浓度及分离电压、进样时间等因素对分离检测的影响。实验采用5.0mmol/L HAc(pH=2.5)+5%乙醇为缓冲溶液,分离电压3.0 kV,在1 min内实现了盐酸洛美沙星的快速分离测定。优化条件下盐酸洛美沙星的线性范围为20.0～250.0μg/mL,检出限为10.0μg/mL(S/N=3),RSD=2.0%,加标回收率为98.6%～103%。     

微芯片毛细管电泳快速测定加替沙星注射液中加替沙星的含量

研究了用微芯片毛细管电泳非接触电导检测系统快速测定加替沙星注射液中加替沙星的方法。对缓冲液的类型、浓度、分离电压以及进样时间等因素进行了优化。最佳条件为:缓冲液5.0 mmol/L HAc,分离电压2.0 kV,进样时间15.0 s。在该条件下,可在1.0 min内实现加替沙星的快速含量测定。线性范围为4.0～150μg/mL,检出限为1.0μg/mL,加标回收率为95.7%～101%,可成功测定注射液中加替沙星的含量。     

Determination of oxalate and citrate in urine by capillary electrophoresis using solid‐phase extraction and capacitively coupled contactless conductivity based on an improved mini‐cell

A new method for the rapid determination of the metabolites oxalate and citrate in urine samples was based on capillary electrophoresis and capacitively coupled contactless conductivity detection coupled with solid‐phase extraction. The detection cell for capacitively coupled contactless conductivity detection was improved with a smaller inner volume (1.5 nL), reduced noise (0.2∼0.5 mV) and better reproducibility and durability. Under optimal conditions, oxalate and citrate can achieve baseline separation within 4 min and the detection limits (S/N = 3) for oxalate and citrate are about 44 and 244 ng/mL, respectively. The overall recovery is between 80.0 and 89.2%. This method offers a better choice for quantitative analysis of strong anions such as oxalate and citrate in diagnostic testing associated with human diseases.     

毛细管电泳及芯片毛细管电泳的电容耦合非接触电导检测

综述了毛细管电泳(CE)及芯片毛细管电泳(MCE)的电容耦合非接触电导检测(Capacitively Coupled Contactless Conductivity detection,C4D)的研究状况;并分别对其装置、检测的影响因素及其应用进行了评述。引用文献81篇。     

毛细管电泳-非接触式电导法直接测定偏硅酸

采用毛细管电泳-电容耦合非接触式电导检测(CE-C<'4>D),以2.4mmol/L KOH+1.6mmol/L K<,2>HPO<,4>+0.4 mmol/L 十六烷基溴化铵(CTMAB)为电泳运行液,融硅石英毛细管(45cm×50μm,有效长度40 cm),负高压分离(-15 kV),偏硅酸可在6.0 min内实现...     

Determination of fluoroacetate and fluoride in blood serum by capillary zone electrophoresis using capacitively coupled contactless conductivity detection

Fluoroacetate is a highly toxic species naturally found in plants and in commercial products (compound 1080) for population control of several undesirable animal species. However, it is non-selective and toxic to many other animals including humans, and thus its detection is very important for forensic purposes. This paper presents a sensitive and fast method for the determination of fluoroacetate in blood serum using capillary electrophoresis with capacitively coupled contactless conductivity detection. Serum blood samples were treated with ethanol to remove proteins. The samples were analyzed in BGE containing 15 mmol/L histidine and 30 mmol/L gluconic acid (pH 3.85). The calibration curve was linear up to 75 μmol/L (R2 =0.9995 for N=12). The detection limit in the blood serum was 0.15 mg/kg, which is smaller than the lethal dose for humans and other animals. Fluoride, a metabolite of the fluoroacetate defluorination, could also be detected for levels greater than 20 μmol/L, when polybrene was used for reversion of the EOF. CTAB and didecyldimethylammonium bromide are not useful for this task because of the severe reduction of the fluoride level. However, no interference was observed for fluoroacetate.     

Elimination of the artefact peaks in capillary electrophoresis determination of glutamate by using organic solvents in sample preparation

Focusing on the demand from the food industry for fast and reliable alternative methods to control the quality of food products, we present in this paper a method for amino acid separation and glutamic acid quantification in complex matrices employing capillary electrophoresis with capacitively coupled contactless conductivity detection. We demonstrate by simulation and experimentally the use of organic solvents in sample preparation to prevent peak splitting and increase stacking in capillary electrophoretic separations of amino acids. Additionally, we obtained results for glutamic acid quantification comparable to those obtained via traditional methods used at industrial sites. We tested premium and low‐cost samples with large variations in their glutamic acid content, which demonstrated the wide range of applicability of the method presented herein. The results of the proposed capacitively coupled contactless conductivity detection based capillary electrophoresis method agreed with those obtained by an enzymatic detector and ultra high performance liquid chromatography coupled to tandem mass spectrometry, considering a confidence level of 95%.     

毛细管电泳场放大进样-高压非接触电导检测测定痕量Zn~(2+)

利用高压电容耦合非接触电导检测器(HV-C4D),结合毛细管电泳场放大进样(FASS),以2-N-吗啡啉乙磺酸(MES)/组氨酸(His)为缓冲溶液,电泳分离测定了Zn2+.考察了样品溶液中MES/His的浓度及电动进样时间对场放大浓缩因子及缓冲溶液浓度对检测灵敏度的影响.在10mmol/LMES/His(pH=4.9)的分离缓冲溶液中,FASS对Zn2+的浓缩因子为1.3×103.Zn2+的浓度在10～1000nmol/L范围内与峰面积有良好线性关系(R=0.9995),检测限为5nmol/L(S/N=3).该方法可用于痕量Zn2+的测定.     

Capillary electrophoretic methods for quality control analyses of pharmaceuticals: A review

Capillary electrophoresis represents a promising technique in the field of pharmaceutical analysis. The presented review provides a summary of capillary electrophoretic methods suitable for routine quality control analyses of small molecule drugs published since 2015. In total, more than 80 discussed methods are sorted into three main sections according to the applied electroseparation modes (capillary zone electrophoresis, electrokinetic chromatography, and micellar, microemulsion, and liposome-electrokinetic chromatography) and further subsections according to the applied detection techniques (UV, capacitively coupled contactless conductivity detection, and mass spectrometry). Key parameters of the procedures are summarized in four concise tables. The presented applications cover analyses of active pharmaceutical ingredients and their related substances such as degradation products or enantiomeric impurities. The contribution of reported results to the current knowledge of separation science and general aspects of the practical applications of capillary electrophoretic methods are also discussed.     

Referenced Capacitively Coupled Conductivity Detector for Capillary Electrophoresis

A dual capacitively coupled contactless conductivity detector for capillary electrophoresis was developed. The two channels are arranged in a bridge configuration so that one of them acts as a reference whose signal is subtracted. This effectively compensates for the baseline conductivity of the separation buffer so that the electronic zero setting is not necessary. Changes in the buffer composition are automatically accounted for, as are temperature drifts. The system is demonstrated for the detection of inorganic model cations in capillary electrophoresis. Besides the use with two separate capillaries, one of which solely serves as reference, it was also found possible to use a single capillary which is looped back through the reference cell.     

Ultrafast capillary electrophoresis method for the simultaneous determination of ammonium and diphenhydramine in pharmaceutical samples

Ammonium and diphenhydramine are active ingredients commonly found in the same pharmaceutical preparations. We report, for the first time, a sub‐minute method for the simultaneous determination of ammonium and diphenhydramine. The method is based on capillary electrophoresis with capacitively coupled contactless conductivity detection. Both analytes can be quantified in a single run (∼80 injections/h) using 30 mmol/L 2‐(N‐morpholino)ethanesulfonic acid and 15 mmol/L lithium hydroxide (pH 6.0) as background electrolyte. The separation by capillary electrophoresis was achieved on a fused‐silica capillary (50 cm total length, 10 cm effective length, and 50 μm inside diameter). The limits of detection were 0.04 and 0.02 mmol/L for ammonium and diphenhydramine, respectively. The proposed method also provided adequate recovery values for spiked samples (100–106 and 97–104% for ammonium and diphenhydramine, respectively). The results obtained with the new capillary electrophoresis method were compared with those of the high‐performance liquid chromatography method for diphenhydramine and the Kjeldahl method for ammonium and no statistically significant differences were found (95% confidence level).     

Determination of carbethopendecinium bromide in eye drops by capillary electrophoresis with capacitively coupled contactless conductivity detection

Antiseptic agent carbethopendecinium bromide (septonex) was determined by capillary electrophoresis with capacitively coupled contactless conductivity detection. Optimal separation of this quaternary ammonium ion was achieved in BGE of pH 7.0 containing 30 mM 2-(N-morpholino)ethanesulfonic acid, 12.5 mg/mL of 2-hydroxypropyl-β-cyclodextrin and 20% v/v of acetonitrile. The separation was performed at 25°C in an uncoated fused silica capillary (50 μm id; total length, 60.5 cm; effective length, 50 cm) at 30 kV. Samples were injected hydrodynamically at 50 mbar for 6 s. For quantitative analysis, L-arginine (500 μg/mL) was used as internal standard. The calibration curve was rectilinear for 25-400 μg/mL of septonex (y=0.0113x-0.0063; r(2)=0.9992). The LOD was 7 μg/mL of septonex (at S/N=3). The run-to-run repeatability (n=6) was characterized by the RSDs of 0.18% for the migration time and 1.96% for the analyte/internal standard peak area ratio. Accuracy tested by recovery experiments at three concentration levels gave recoveries of 100.27-104.22% with RSD ≤2.19%. The method was successfully applied to the assay of carbethopendecinium bromide in eye drops. Quaternary ammonium ions having structure and size close to that of carbethopendecinium may not be resolved from the analyte.     

Determination of muscle relaxants pancuronium and vecuronium bromide by capillary electrophoresis with capacitively coupled contactless conductivity detection

A novel capillary electrophoretic method for the separation of pancuronium (PM) and vecuronium (VM) ions utilizing capacitively coupled contactless conductivity detection was devised and validated. The separation was carried out in bare fused-silica capillaries (50 μm id, 75/45 cm) at 25°C. Optimal BGE was 50 mM borate buffer of pH 9.5 containing 12.5 mg/mL of (2-hydoxypropyl)-γ-CD. The samples were injected hydrodynamically at 1000 mbar for 3 s. Separation was performed at +30 kV. Under such conditions the PM and VM were base-line resolved and the separation took < 4 min. For quantification phenyltrimethylammonium iodide was used as internal standard. Calibration curves were linear for both pancuronium bromide (PMB) and vecuronium bromide (VMB) in the range 25-250 μg/mL with r> 0.9968. The limits of detection were 7 and 6?μg/mL for PMB and VMB, respectively. The accuracy tested by recovery experiment at three concentration levels of added PMB and VMB was satisfactory (95.7-102.7%, n =3, with RSD < 2.61%). The method was successfully applied to the assay of PMB and VMB in commercial injection solutions.     

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...     

Fast determination of codeine,orphenadrine, promethazine,scopolamine, tramadol,and paracetamol in pharmaceutical formulations by capillary electrophoresis

Paracetamol is an active ingredient commonly found in pharmaceutical formulations in combination with one of the following compounds: codeine, orphenadrine, promethazine, scopolamine, and tramadol. In this work, we propose a unique analytical method for determination of these active ingredients in pharmaceutical samples. The method is based on capillary electrophoresis with capacitively coupled contactless conductivity detection. The separation was achieved on a fused silica capillary (50 cm total length, 40 cm effective length, and 50 μm id) using an optimized background electrolyte composed of 20 mmol/L β‐alanine/4 mmol/L sodium chloride/4 μmol/L sodium hydroxide (pH 9.6). Each sample can be analyzed in a single run (≤2 min) and the limits of detection were 2.5, 0.62, 0.63, 2.5, 15, and 1.6 μmol/L for scopolamine, tramadol, orphenadrine, promethazine, codeine, and paracetamol, respectively. Recovery values for spiked samples were between 94 and 104%.     

Contactless conductivity detection for analytical techniques: Developments from 2016 to 2018

The publications concerning capacitively coupled contactless conductivity detection for the 2‐year period from mid‐2016 to mid‐2018 are covered in this update to the earlier reviews of the series. Relatively few reports on fundamental investigations or new designs have appeared in the literature in this time interval, but the development of new applications with the detection method has continued strongly. Most often, contactless conductivity measurements have been employed for the detection of inorganic or small organic ions in conventional capillary electrophoresis, less often in microchip electrophoresis. A number of other uses, such as detection in chromatography or the gauging of bubbles in streams have also been reported.