用带电子捕获检测的气相色谱法定量生物流体中的新型抗心律失常药醋酸氟卡尼。

Quantitation of flecainide acetate, a new antiarrhythmic agent, in biological fluids by gas chromatography with electron-capture detection.

作者信息

Johnson J D, Carlson G L, Fox J M, Miller A M, Chang S F, Conrad G J

出版信息

J Pharm Sci. 1984 Oct;73(10):1469-71. doi: 10.1002/jps.2600731037.

Abstract

A sensitive and selective gas chromatographic (GC) method for the quantitation of flecainide acetate, a new antiarrhythmic agent, was developed. The unchanged drug and internal standard were separated from biological fluids by a sequence of solvent extractions and then the drug was derivatized. The pentafluorobenzamide derivatives were chromatographed on a 3% SP-2250 glass column and detected with a nickel-63 electron-capture detector. By this method, greater than or equal to 12.5 ng of flecainide/mL can be quantitated in a 1-mL sample of plasma, saliva, or urine. The intraday precision, expressed as the RSD, at plasma levels of 12.5, 25, 50, 100, 200, 300, 400, and 600 ng/mL was 3.4, 6.2, 5.3, 6.4, 1.0, 1.6, 2.0, and 0.5%, respectively; the accuracy, expressed as relative error at these levels was -24.6, -6.9, -6.0, +0.6, +3.8, -0.3, +2.4, and -1.4%, respectively. The interday precision at these levels was 13.8, 13.0, 5.7, 7.6, 8.3, 6.1, 9.0, and 5.4%, respectively. Several other antiarrhythmic agents and one beta-blocker, which might be administered concurrently with flecainide acetate, do not interfere with the assay.

摘要

已开发出一种灵敏且具选择性的气相色谱（GC）法，用于定量测定新型抗心律失常药物醋酸氟卡尼。通过一系列溶剂萃取将未变化的药物和内标物从生物流体中分离出来，然后对药物进行衍生化处理。五氟苯甲酰胺衍生物在3% SP - 2250玻璃柱上进行色谱分离，并用镍 - 63电子捕获检测器进行检测。通过该方法，在1 mL血浆、唾液或尿液样本中，可定量测定浓度大于或等于12.5 ng/mL的醋酸氟卡尼。在血浆浓度为12.5、25、50、100、200、300、400和600 ng/mL时，日内精密度（以相对标准偏差表示）分别为3.4%、6.2%、5.3%、6.4%、1.0%、1.6%、2.0%和0.5%；在这些浓度下，准确度（以相对误差表示）分别为 - 24.6%、 - 6.9%、 - 6.0%、 + 0.6%、 + 3.8%、 - 0.3%、 + 2.4%和 - 1.4%。在这些浓度下的日间精密度分别为13.8%、13.0%、5.7%、7.6%、8.3%、6.1%、9.0%和5.4%。其他几种可能与醋酸氟卡尼同时给药的抗心律失常药物和一种β受体阻滞剂不会干扰该测定。