微流控芯片毛细管电泳激光诱导荧光检测法测定片剂中盐酸美西律的含量

建立了微流控芯片毛细管电泳激光诱导荧光检测法测定片剂中盐酸美西律含量的方法,对衍生条件和电泳条件进行了系统的考察。盐酸美西律经异硫氰酸荧光素(FITC)40℃衍生6h,以20 mmol/L硼砂为电泳缓冲溶液,进样30s后,分离电压2000V,可在1 min内完成一次检测。方法的检出限为0.022 mg/L、线性范围0.108～1.079 mg/L、相关系数0.994,加标回收率为99.7%～102.3%,方法适用于盐酸美西律的检测和质量控制。     

Determination and Pharmacokinetics of Mexiletine in Rabbit Plasma by Gas Chromatography with Mass Spectrometry

This paper describes a gas chromatography/mass spectrophotometry method for determination of mexiletine in rabbit plasma. Mexiletine and internal standard metoprolol were extracted from rabbit plasma with a mixture of ethylacetate and diethylether at basic pH with liquid-liquid extraction. Calibration curves were linear over the concentration range 45–2000 ng/mL. Intra- and inter-day precision (relative standard deviation) for mexiletine in rabbit plasma were less than 6.9%, and accuracy (relative error) was better than 6.8%. Recovery of mexiletine from rabbit plasma averaged 92.6%. This method was successfully applied to six rabbits which had given an oral capsule of 200 mg mexiletine.     

<Emphasis Type="Italic">S,S,S</Emphasis>-Tris(2-ethylhexyl) phosphorotrithioate as an effective solvent mediator for a mexiletine-sensitive membrane electrode

S,S,S-Tris(2-ethylhexyl) phosphorotrithioate proved to be an effective solvent mediator for constructing a mexiletine-sensitive membrane electrode in combination with an ion-exchanger, sodium tetrakis[3,5-bis(2-methoxyhexafluoro-2-propyl)phenyl]borate. Among a series of phosphorus compounds containing phosphoryl (P=O) groups, this solvent mediator showed the highest sensitivity to mexiletine in phosphate-buffered physiological saline containing 0.15 mol L⁻¹ NaCl and 0.01 mol L⁻¹ NaH₂PO₄/Na₂HPO₄ (pH 7.4), giving a detection limit of 2 × 10⁻⁶ mol L⁻¹ with a slope of 58.8 mV decade⁻¹. This is the best reported detection limit of any mexiletine-sensitive electrode developed to date. Owing to its high selectivity toward inorganic cations, the electrode was used to determine the level of mexiletine in saliva, the monitoring of which is quite effective for controlling the dose of this drug noninvasively. The mexiletine concentrations determined with the mexiletine-sensitive electrode compared favorably with those determined by high-performance liquid chromatography.     

Retention Behavior of Anti-Arrhythmic Drugs on the Chromolith Performance RP 18 Column. Liquid Chromatographic Determination of Mexiletine Hydrochloride

The retention behavior in liquid chromatography of a series of anti-arrhythmic drugs is described. Chromatographic analysis was performed on a Chromolith Performance ODS column with acetonitrile–phosphate buffer mixtures as mobile phases. The effects of the proportion of organic solvent (from 20 to 90%), phosphate buffer pH (from 2.73 to 7.5), flow rate (from 1 to 6 mL min^–1), and isocratic or gradient elution on the retention of the compounds was studied. Mexiletine hydrochloride was determined in the pure substance and in capsules by isocratic liquid chromatography with 20:80 (v/v) acetonitrile–0.007 M phosphate buffer, pH 3.0, as mobile phase at 2 mL min^–1. Methanol was found to be a suitable solvent for extraction of the active substance from capsules. The calibration plot was linear (r=0.9999) in the concentration range 1.0 to 6.0 g mL^–1. The proposed method is selective, precise (RSD=0.37%), and accurate (recovery=100.08%).Revised: 28 January and 2 March 2004     

A Simplified Extraction for Mexiletine from Serum and Analysis by High Performance Liquid Chromatography

Abstract

The analysis of mexiletine by High Performance Liquid Chromatography (HPLC) requires organic extraction followed by evaporation of the organic solvent. Calibration curves must be prepared using standards in drug-free serum. This procedure has been simplified by using a back extraction of the mexiletine from serum. Calibration curves can then be more quickly prepared since good agreement can be obtained using standards in hydrochloric acid (HCl) instead of having to prepare standards in serum with the time-consuming necessity of having to extract these standards.     

A simple high-performance liquid chromatographic determination of mexiletine in human plasma at therapeutic levels

Summary A method for the quantitative determination of mexiletine in human plasma by high-performance liquid chromatography has been described. The plasma samples are buffered to pH 12 and extracted on Clin-Elut columns with diethylether-ethylacetate (1:1), after addition of the internal standard, the 2,4,6 methyl analogue of mexiletine. The minimum detectable amount of mexiletine is 50 ng in 0.5 ml plasma. Recovery is between 96–114% and the relative standard deviation at 1.5 ml^–1 level of mexiletine is 2.1% Accurate determinations of human plasma levels were performed after oral or intravenous treatment.Part of the work was presented at the 29. Kongreß der Deutschen Gesellschaft für Laboratoriumsmedizin, Hamburg 1985.     

Nucleophilic substitution of (sulfonyloxymethyl)aziridines: an asymmetric synthesis of both isomers of mexiletine

The nucleophilic substitution reactions of 1-[1′(R)-α-methylbenzyl]-(2R)- and (2S)-(sulfonyloxymethyl)aziridines were carried out with various nucleophiles including N₃⁻, MeO⁻, CN⁻, SCN⁻, and diarylcuprates. The reaction pathway is influenced by the stereochemistry of the substrates, nucleophiles, and also the structure of the leaving groups. When the reaction site is less sterically hindered for the reactive nucleophiles to approach to the substrate 1-[1′(R)-α-methylbenzyl]-(2S)-(p-toluenesulfonyloxymethyl)aziridines, product is obtained as a single isomer while all the other starting materials afford a mixture of two isomers from two different reaction pathways. Application of this method enabled us to prepare both isomers of orally effective antiarrhythmic agent mexiletine.     

Synthesis of dinitrophenyl-l-Pro-N-hydroxysuccinimide ester and four new variants of Sanger's reagent having chiral amines and their application for enantioresolution of mexiletine using reversed-phase high-performance liquid chromatography

Four chiral derivatizing reagents (CDRs) having enantiomerically pure amines and two CDRs namely, [N-succinimidyl-(S)-2-(6-methoxynaphth-2-yl)propionate], and [dinitrophenyl-l-Pro-N-hydroxysuccinimide ester, DNP-l-Pro-SU] were synthesized and were used to prepare diastereomers of (R,S)-mexiletine (MEX); these were separated by reversed-phase high-performance liquid chromatography (RP-HPLC). The method was validated for linearity, accuracy, limit of detection (LOD) and limit of quantification (LOQ).     

衍生化-离子液体萃取分光光度法测定盐酸美西律

盐酸美西律与1,2-萘醌-4-磺酸钠在pH=9.0的介质中反应生成一种橙红色衍生物,该衍生物能被离子液体所萃取,其最大吸收波长发生较大幅度红移,吸光度显著增强。据此建立了高选择性的测定盐酸美西律的衍生化-离子液体萃取分光光度法。萃取后的衍生物在448 nm处的表观摩尔吸光系数ε为2.69×104L·mol-1·cm-1。盐酸美西律浓度在0.2～5.4μg·mL-1范围内符合比耳定律,相关系数为0.9994,检出限为0.067μg·mL-1。该方法已用于药物制剂及尿样中盐酸美西律的测定,其回收率分别为99.5%～100.7%和96.6%～101.5%。