Chiral separation of bupivacaine enantiomers by capillary electrophoresis partial-filling technique with human serum albumin as chiral selector

Capillary electrophoresis (CE) is a powerful technique for enantiomer separations due to its intrinsic high separation efficiencies, speed of analysis, low reagent consumption and small sample requirements. However, some chiral selectors present strong background UV absorption providing high detection limits. The present paper deals with the application of the partial-filling technique to the separation of bupivacaine enantiomers by capillary electrophoresis using human serum albumin (HSA) as chiral selector. In this procedure the cationic surfactant cetyltrimethylammonium bromide (CTAB) was used as a dinamic capillary coating in order to reduce the electro-osmotic flow and detect both bupivacaine enantiomers out of the chiral selector plug. Several experimental conditions such as CTAB concentration, pH, HSA concentration and plug length, background electrolyte concentration, temperature and voltage were studied. Under the selected conditions it is possible to detect the separated enantiomers out of the HSA plug in less than 4 min using 50 mM Tris pH 8 as background electrolyte with 50 microM CTAB, at 30 degrees C and using a separation voltage of 25 kV. The proposed methodology was then validated for analytical purposes and applied to the analysis of pharmaceutical preparations commercially available. The results obtained with the proposed methodology were in good agreement with those declared by the manufacturers. The simplicity, sample throughput, accuracy, reproducibility and low cost of the proposed method make it suitable for the control of the enantiomeric composition of bupivacaine in pharmaceuticals.     

Determination of bupivacaine and metabolites in rat urine using capillary electrophoresis with mass spectrometric detection

A method using capillary electrophoresis-mass spectrometry (CE-MS) was developed for the structural elucidation of bupivacaine and metabolites in rat urine. Prior to CE-MS analysis, solid-phase extraction (SPE) was used for sample cleanup and preconcentration purposes. Exact mass and tandem mass spectrometric (MS/MS) experiments were performed to obtain structural information about the unknown metabolites. Two instruments with different mass analyzers were used for mass spectrometric detection. A quadrupole time-of-flight (Q-TOF) and a magnetic sector hybrid instrument were coupled to CE and used for the analysis of urine extracts. Hydroxybupivacaine as well as five other isomerically different metabolites were detected including methoxylated bupivacaine.     

重度子痫前期产妇剖宫产布比卡因蛛网膜下腔阻滞麻醉适合剂量的临床研究

目的 探讨重度子痫前期产妇剖宫产重比重布比卡因蛛网膜下腔阻滞麻醉（腰麻）的适合剂量。方法 选取200例重度子痫前期产妇,ASAⅠ级或Ⅱ级,按随机数字表法分为4组,每组各50 例,相应各组鞘内注入布比卡因剂量分别为10、8、6 及4mg,并混合2.5μg 舒芬太尼。选择L3~4行腰硬联合穿刺,注药10min 后记录麻醉平面。根据结果进行Probit 回归分析,计算布比卡因腰麻的ED50和ED95。观察各组利多卡因及去氧肾上腺素的用量、肌松效果及患者麻醉满意度,观察各组术中并发症以及新生儿的Apgar 评分和脐动脉pH。结果 重度子痫前期患者腰麻剖宫产布比卡因ED50 和ED95分别为：6.51（95%CI：5.81～7.01）和8.68（95%CI：7.96～10.26）。4 组患者10min 后麻醉平面的差异均有统计学意义（均P＜0.05）。4mg 组利多卡因用量高于其他3组,差异有统计学意义（P＜0.05）。8mg 组、10mg 组去氧肾上腺素的用量高于其他两组,差异均有统计学意义（均P＜0.05）。低血压的发生率8mg 组、10mg 组高于其他两组,差异均有统计学意义（均P＜0.05）。４ 组间其他不良反应恶心、呕吐、寒战以及心动过缓发生率的差异无统计学意义（P＞0.05）。4 组胎儿娩出后1、5min Apgar 评分及脐动脉血气分析的结果差异均无统计学意义（均P＞0.05）。结论 重度子痫前期产妇剖宫产鞘内注入6mg 布比卡因混合2.5μg舒芬太尼,必要时辅以硬膜外麻醉,麻醉效果确切,血流动力学稳定,适合该类患者手术麻醉。     

毛细管电泳电致化学发光检测血浆中布比卡因

布比卡因是一种外科局部麻醉剂,使用过量会导致中枢神经系统和心脏血管系统中毒^[1],可引起心脏停博.高效液相色谱和毛细管电泳(CE)^[2]是该药常用的检测方法.     

New Ion-Selective Electrodes for Determination of Bupivacaine and Oxybuprocaine

Abstract

PVC membrane electrodes selective for hydrochlorides of the anaesthetics bupivacaine (BpC) and oxybuprocaine (ObC) are prepared. The electrodes have a near Nernstian slope (58 mV for BpC and 51 mV for ObC electrodes) over the range of 1.6 × 10^?5-10^?1M and 1.3 × 10^?1M for BpC and ObC electrodes, respectively. The change in pH of the test solution within the ranges 2.5–6.0 and 3.0–7.4 does not affect the EpC-and ObC-electrodes, respectively. The electrodes have very long life times (10 days for BpC, and 3 months for ObC) and exhibit good seletivity for the investigated compounds with respect to a large number of inorganic cations and organic substances of biological importance. The isothermal coefficients of the electrodes are calculated from the standard electrode potentials at different temperatures. BpC and ObC are determined successfully in some pharmaceutical preparations using the calibration graph technique and potentiometric titration.     

原子吸收光谱法间接测定盐酸布比卡因

提出了在Ｎ，Ｎ－二甲基甲酰胺（ＤＭＦ）存在下，用二氯乙烷萃取盐酸布比尔因与钴硫氰酸根生成的离子对缔合物，经反萃取后，用原子吸收光谱法测定反萃取液中的Ｃｏ＾２＋量间接确定盐酸布比卡因含量的新方法，本法在０．０５～１．３０ｇ／Ｌ范围内呈线良好线性关系（ｒ＝０．９９９９），回收率在９８％～１０３％的范围内，用于实际样品测定获得良好效果。     

On‐line preconcentration strategy for the simultaneous quantification of three local anesthetics in human urine using CZE

The simultaneous determination of usually employed anesthetics (procaine, lidocaine, and bupivacaine) has been developed and validated using CE with ultraviolet detection at 212 nm. The separation of these three drugs has been achieved in less than 7 min, using a temperature of 25ºC and 25 kV, with a 150 mM citrate buffer (pH 2.5) as BGE. Field‐amplified sample injection (FASI) has been used for on‐line sample preconcentration. Ultrapure water and ACN 50/50 (v/v) mixture gave the greatest enhancement factor when it was employed as an injection solvent. Injection voltage and time were optimized, being 13 kV and 13 s, the optimum values, respectively. To avoid the possible irreproducibility associated with the electrokinetic injection, an internal standard such as tetracaine, was employed. The instrumental detection limits (LOD S/N = 3) for the compounds ranged between 2.6 and 7.0 μg L⁻¹ and the quantitation limits (LOQ S/N = 10) between 37.8 and 55.9 μg L⁻¹. The detection limits obtained in real human urine samples ranged between 55.2 and 83.6 μg L⁻¹ and the quantitation limits between 196.0 and 276.0 μg L⁻¹. The proposed method has demonstrated its applicability to the analysis of these local anesthetics in urine samples without any pretreatment, allowing the rapid determination of these target analytes.     

毛细管电泳法同时测定血浆中的美西律、利多卡因和布比卡因的浓度

采用毛细管电泳法同时测定血浆中关西律、利多卡因和布比卡因的浓度。取0．5mL血浆，用乙醚提取后吹干，重组后进样于毛细管电泳仪进行分离测定。电泳条件：分离用缓冲液为75mmol／L NaH2PO4溶液（pH3．0），温度30℃，运行电压26kV，紫外检测，波长200nm，压力进样5S。本法在0．1～4．0μg／mL范围内线性关系和精密度良好，方法回收率在96％～105％之间，检出限均为0．02μg／mL，可满足临床监测需要。     

Physicochemical characterization of drug-cyclodextrin complexes prepared by supercritical carbon dioxide and by conventional techniques

The objective of this study was to investigate the effectiveness of supercritical carbon dioxide (SC CO₂) technique for preparing solid complexes between β-cyclodextrin and three local anesthetic agents (benzocaine, bupivacaine, and mepivacaine) by comparing it to more traditional methods such as kneading, co-evaporation, co-grinding, and sealed-heating. Effects of variation of experimental conditions, i.e. temperature, pressure and exposure time, on the products prepared by SC CO₂ method were also examined. The products obtained were characterized by powder X-ray diffractometry and Fourier transform infrared spectroscopy, and tested for dissolution properties. Results suggested the possibility of complex formation between β-cyclodextrin and the three anesthetic agents, and indicated that it was influenced by the preparation technique. The co-grinding method was the only one resulting in completely amorphous products for all three drugs. Almost amorphous products, with only limited residual crystallinity, were obtained by co-evaporation and kneading techniques, while SC CO₂ and sealed-heating methods gave rise to more crystalline systems. As for the SC CO₂ method, temperature (for benzocaine and bupivacaine) or exposure time (for mepivacaine) had significant effects on the solid-state properties of the final products. Dissolution studies indicated that all the examined methods were more effective than the simple physical mixing in improving drug dissolution properties, but the different rank orders observed for the different drugs suggested that there is no general rule for the selection of the most effective preparation method, which depends on the type of drug-Cyd system considered. Nevertheless, in all cases, products obtained by the SC CO₂ method showed satisfactory dissolution properties.     

钴硫氰酸根离子缔合－萃取光度法测定盐酸布比卡因

本文提出了在Ｎ，Ｎ－二甲基甲酰胺（ＤＭＦ）存在下，用萃取光度法研究了盐酸布比卡因与钴硫氰酸根络阴离子生成的离子缔合物的实验条件及反应机理，并用于实际样品的测定，获得了良好的效果。实验结果表明，由于ＤＦＭ对二氯甲烷的协同作用，使反应体系较之单一溶剂萃取更稳定、更灵敏。