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通过与4-氯-7-硝基苯并-2-恶唑-1,3-二唑衍生化,采用荧光分光光度法测定剂型和加标血浆样品中的氨己烯酸和加巴喷丁。

Spectrofluorimetric determination of vigabatrin and gabapentin in dosage forms and spiked plasma samples through derivatization with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole.

作者信息

Hassan E M, Belal F, Al-Deeb O A, Khalil N Y

机构信息

King Saud University, College of Pharmacy, Department of Pharmaceutical Chemistry, Riyadh, Saudi Arabia.

出版信息

J AOAC Int. 2001 Jul-Aug;84(4):1017-24.

Abstract

A highly sensitive and specific method is proposed for the determination of vigabatrin (I) and gabapentin (II) in their dosage forms and spiked human plasma. The method is based on coupling the drugs with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole in borate buffer at pH 7.1 and measuring the resulting fluorescence at 532 nm after excitation at 465 nm. The fluorescence intensity was a linear function of the concentration of the drugs over the ranges of 1.3-6.5 and 1.7-8.5 microg/mL for I and II, respectively. Minimum detectability values were 0.54 microg/mL (4.2 x 10(-6)M) and 0.97 microg/mL (5.7 x 10(-6)M) for I and II, respectively, under the described conditions. The proposed method was successfully applied to the determination of the 2 drugs in their dosage forms, and the percent recoveries +/- standard deviation (SD) were 104.53 +/- 1.2 and 100.00 +/- 1.32 of the label claim for I and II, respectively. The method was further applied to the determination of vigabatrin in spiked plasma samples. The percent recovery +/- SD was 101.58 +/- 2.68. Interference from endogenous alpha-amino acids was overcome through selective complexation with freshly prepared Cu(OH)2. The interference likely to be encountered from co-administered drugs, such as carbamazepine, cimetidine, clonazepam, clopazam, phenobarbital, valproic acid, and lamotrigine, was also studied. A reaction pathway is suggested.

摘要

本文提出了一种高灵敏度和高特异性的方法,用于测定其剂型和加标人血浆中的氨己烯酸(I)和加巴喷丁(II)。该方法基于在pH 7.1的硼酸盐缓冲液中,将药物与4-氯-7-硝基苯并-2-恶唑-1,3-二唑偶联,并在465 nm激发后,于532 nm处测量产生的荧光。荧光强度分别在1.3 - 6.5和1.7 - 8.5 μg/mL范围内,是I和II药物浓度的线性函数。在所描述的条件下,I和II的最低检测值分别为0.54 μg/mL(4.2×10⁻⁶ M)和0.97 μg/mL(5.7×10⁻⁶ M)。所提出的方法成功应用于其剂型中两种药物的测定,I和II的回收率±标准偏差(SD)分别为标示量的104.53±1.2和100.00±1.32。该方法进一步应用于加标血浆样品中氨己烯酸的测定。回收率±SD为101.58±2.68。通过与新制备的Cu(OH)₂选择性络合,克服了内源性α-氨基酸的干扰。还研究了可能来自共同给药药物(如卡马西平、西咪替丁、氯硝西泮、氯帕唑、苯巴比妥、丙戊酸和拉莫三嗪)的干扰。提出了一种反应途径。

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