Tzanavaras Paraskevas D, Zacharis Constantinos K, Rigas Pantelis
Laboratory of Analytical Chemistry, Department of Chemistry, Aristotelian University of Thessaloniki, GR-54124 Thessaloniki, Greece.
J Pharm Biomed Anal. 2008 Dec 1;48(4):1254-60. doi: 10.1016/j.jpba.2008.09.017. Epub 2008 Sep 17.
The first automated method for the determination of mexiletine hydrochloride - an antiarrhythmic agent - is reported. The method is based on the reaction of the analyte with o-phthalaldehyde (OPA) in the presence of sulfite in basic medium using a sequential injection (SI) manifold. The reaction product was monitored spectrofluorimetrically (lambda(ex)=350 nm/lambda(em)=446 nm). A simple and effective on-line dilution approach was adopted in order to expand the linearity and apply the method to assay, dosage uniformity and dissolution tests with minimum sample preparation. Chemical (pH, amount concentrations of OPA and sulfite) and instrumental variables (temperature, flow rate, injection volumes, etc.) that affected the determination were studied. The developed assay was validated in terms of linearity, range, limits of detection (LOD=3.4 mg L(-1)) and quantitation (LOQ=10 mg L(-1)), accuracy, precision (R.S.D.<3.4%) and selectivity. The method was applied successfully to the quality control of a mexiletine-containing formulation. The results were in good agreement with the US pharmacopoeia HPLC method.
报道了第一种用于测定盐酸美西律（一种抗心律失常药物）的自动化方法。该方法基于在碱性介质中，分析物与邻苯二甲醛（OPA）在亚硫酸盐存在下的反应，采用顺序注射（SI）流路。反应产物通过荧光分光光度法监测（激发波长λ(ex)=350 nm/发射波长λ(em)=446 nm）。采用了一种简单有效的在线稀释方法，以扩展线性范围，并在最少样品制备的情况下将该方法应用于含量测定、剂量均匀度和溶出度测试。研究了影响测定的化学变量（pH值、OPA和亚硫酸盐的量浓度）和仪器变量（温度、流速、进样体积等）。所开发的含量测定方法在线性、范围、检测限（LOD=3.4 mg L(-1)）和定量限（LOQ=10 mg L(-1)）、准确度、精密度（R.S.D.<3.4%）和选择性方面进行了验证。该方法成功应用于含美西律制剂的质量控制。结果与美国药典HPLC方法高度一致。
