Katsu T, Mori Y, Furuno K, Gomita Y
Faculty of Pharmaceutical Sciences, Okayama University, Tsushima-naka, Japan.
J Pharm Biomed Anal. 1999 Mar;19(3-4):585-93. doi: 10.1016/s0731-7085(98)00260-x.
Response characteristics of mexiletine-sensitive membrane electrodes based on crown ether and ion-exchanger were examined in a physiological saline in order to find an electrode suitable for determining concentrations of this drug under physiological conditions. Among various crown ethers screened, 4',4"(5")-di-tert-butyldicyclohexano-18-crown6 showed the highest sensitivity to mexiletine in physiological saline containing 0.15 M NaCl and 5 mM 4-(2-hydroxyethyl)-2-piperazineethanesulfonic acid (Hepes) NaOH (pH 7.4). However, the detection limit of 30 microM was 10 times higher than that of 3 microM observed with the electrode based on an ion-exchanger, sodium tetrakis[3,5-bis(2-methoxyhexafluoro-2-propyl)phenyl]borate. Having high selectivity against inorganic cations such as Na+ or K+, the electrode using the ion-exchanger enabled us 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 electrode compared favourably with those determined by high-performance liquid chromatography which requires an additional procedure to extract mexiletine from saliva.
为了找到一种适合在生理条件下测定美西律浓度的电极，研究了基于冠醚和离子交换剂的美西律敏感膜电极在生理盐水中的响应特性。在筛选的各种冠醚中，4',4"(5")-二叔丁基二环己基-18-冠-6在含有0.15M氯化钠和5mM 4-(2-羟乙基)-2-哌嗪乙磺酸（Hepes）氢氧化钠（pH 7.4）的生理盐水中对美西律表现出最高的灵敏度。然而，30微摩尔的检测限比基于离子交换剂四[3,5-双(2-甲氧基六氟-2-丙基)苯基]硼酸钠的电极所观察到的3微摩尔高10倍。使用该离子交换剂的电极对诸如Na+或K+等无机阳离子具有高选择性，使我们能够测定唾液中美西律的水平，对其进行监测对于无创控制该药物的剂量非常有效。用美西律电极测定的美西律浓度与用高效液相色谱法测定的浓度相比具有优势，高效液相色谱法需要额外的步骤从唾液中提取美西律。
