Liquid chromatographic determination of oxcarbazepine and its metabolites in plasma of epileptic patients after solid-phase extraction

A method based on high-performance liquid chromatography with UV detection in combination with solid-phase extraction for sample pretreatment has been developed for the simultaneous analysis of the antiepileptic drug oxcarbazepine and its main metabolites in human plasma. The extraction of the analytes from plasma samples was carried out by means of a selective solid-phase extraction procedure using hydrophilic-lipophilic balance cartridges. The separation was obtained on a reversed-phase column (C(18), 150x4.6 mm I.D., 5 micrometer) using a phosphate buffer-acetonitrile-methanol-triethylamine mixture (final apparent pH* 3.5) as the mobile phase. Under these chromatographic conditions, oxcarbazepine and its metabolites 10,11-dihydro-10-hydroxycarbamazepine, 10,11-dihydro-10,11-dihydroxycarbamazepine and the internal standard are baseline separated in less than 9 min. The extraction yield values were >94% for all analytes and the precision, expressed by the RSD%, was in the low percentage range. For the entire method, including sample pre-treatment and HPLC determination, the linearity of the calibration lines, expressed by the linear correlation coefficient, was better than 0.995; the limit of quantitation was 15 ng ml(-1). The method was applied to plasma samples from patients undergoing chronic treatment with oxcarbazepine, both in monotherapy and in polytherapy. Based on the analytical parameters precision, accuracy, limit of quantitation and analysis time the method is suitable for routine application in therapeutic drug monitoring.     

Determination of oxcarbazepine and its metabolites in postmortem blood and hair by means of liquid chromatography with mass detection (HPLC/APCI/MS)

A typical use of hair analysis in forensic toxicology is the documentation of previous drug administration. This is illustrated in a suicidal death of a 58-year-old epileptic patient who was treated with oxcarbazepine and probably with levomepromazine. The toxicological analysis carried out by HPLC/APCI/MS included also the hair (6 cm length) besides postmortem blood. The method was validated for levomepromazine, oxcarbazepine (OXCBZ) and its two metabolites, 10-hydroxycarbazepine (CBZ-10OH) and trans-diol-carbazepine (CBZ-diOH) in various biological matrices. The analysis of the postmortem blood indicated oxcarbazepine and its two main metabolites were present at therapeutic concentrations; levomepromazine was detected at a fatal concentration. In three 2-cm segments of hair, oxcarbazepine and its two metabolites were detected; however, levomepromazine was not detected in this specimen. As a result of complex chemical-toxicological investigation it was confirmed the information that the decedent. was an epileptic patient and was treated with oxcarbazepine for at least 6 months before death. In addition, he took a toxic dose of levomepromazine in order to commit suicide. The analysis revealed differences between the concentration levels of oxcarbazepine and its active metabolite CBZ-10OH in postmortem specimens and hair, suggesting different mechanisms of penetration of metabolites and their precursors into this matrix.     

奥卡西平与丙戊酸钠对癫痫患者血液学指标、认识功能及生活质量的影响

目的:探讨奥卡西平与丙戊酸钠对癫痫患者血液学指标、认识功能及生活质量的影响。方法:将2015年6月至2017年5月我院接诊的癫痫患者98例纳入本研究,随机分为观察组(n=49)和对照组(n=49),对照组给予丙戊酸钠治疗。观察组给予奥卡西平治疗。比较两组同型半胱氨酸(Hcy)、不对称二甲基精氨酸(ADMA)水平、简明精神状态检查量表(MMSE)评分、癫痫患者生活质量量表(QOLIE)评分,并比较两组不良反应发生情况。结果:治疗后两组患者Hcy、ADMA水平均高于治疗前,差异有统计学意义(P0.05),但治疗前和治疗后两组患者Hcy、ADMA水平组间比较差异均无统计学意义(P0.05)。观察组治疗后MMSE评分高于治疗前和对照组(P0.05);对照组治疗前后MMSE评分对比,差异无统计学意义(P0.05)。两组患者治疗后QOLIE各项评分高于治疗前(P0.05),观察组治疗后精力/疲乏、认知功能、药物影响等评分以及总评分高于对照组(P0.05)。观察组不良反应发生率为4.08%,与对照组的10.20%比较差异无统计学意义(P0.05)。结论:奥卡西平与丙戊酸钠治疗癫痫患者均可升高其Hcy、ADMA水平,无严重不良反应发生,而奥卡西平在改善癫痫患者的认知功能和生活质量等方面优于丙戊酸钠。     

奥卡西平对偏头痛大鼠三叉神经节神经元钙电流的影响*

目的:研究奥卡西平(Oxcarbazepine,OXC)对大鼠三叉神经节神经元钙电流的调控作用。方法:SD大鼠随机分为3组(n=8):生理盐水组(NS组),致炎剂组(IS组),OXC预防组。应用膜片钳技术,采用全细胞记录方式,观察OXC对偏头痛大鼠急性分离的三叉神经节的高电压激活钙电流(HVA-ICa)的调控作用。结果:OXC能够抑制钙电流,使钙电流的激活曲线向去极化方向移动,使钙电流的失活曲线向超级化方向移动。结论:OXC可能通过抑制钙离子进入细胞膜,来预防偏头痛的发作。同时OXC可能对外周神经系统及伤害感受的传入的兴奋性起到调控作用。     

丙戊酸钠联合奥卡西平治疗小儿癫痫的疗效及对患儿脑电图、认知功能和血清神经因子的影响

摘要 目的：评价丙戊酸钠联合奥卡西平治疗小儿癫痫的疗效及对患儿脑电图、认知功能和血清神经因子的影响。方法：选入2019年1月~2022年12月收治的癫痫患儿104例,根据治疗方法不同分为单药组（丙戊酸钠治疗）和联合组（丙戊酸钠+奥卡西平治疗）,各52例。评价两组的临床疗效、脑电图、认知功能、血清神经因子等指标,并进行统计比较。结果：联合组治疗后癫痫发作频率及每次持续时间显著低于单药组（P<0.05）,EEG显示痫样放电率、总异常亦明显低于单药组（P＜0.05）;联合组治疗总有效率94.23%,明显高于单药组的71.15%（P<0.05）;两组治疗后WISC-CR量表VIQ、PIQ和FIQ评分均较治疗前明显升高（P<0.05）,而联合组升高幅度更大,与单药组差异显著（P<0.05）;治疗前,两组血清BDNF、NSE和S-100β蛋白无明显差异（P＞0.05）,而治疗后,联合组血清BDNF水平明显高于单药组、NSE和S-100β水平显著低于单药组（P＜0.05）;两组不良反应总发生率无差异（P＞0.05）。结论：丙戊酸钠联合奥卡西平治疗小儿癫痫疗效较好,可有效缓解临床症状,控制脑部异常放电,改善认知功能,调节血清神经因子水平,且安全性良好。