高效液相色谱法同时测定苯巴比妥、苯妥英、卡马西平、茶碱的血药浓度

目的:建立以高效液相(HPLC)色谱法同时测定苯巴比妥、苯妥英、卡马西平、茶碱血药浓度的方法.方法:苯巴比妥、苯妥英、卡马西平、茶碱血浆样品,经二氯甲烷提取,测定苯巴比妥、卡马西平、茶碱的血药浓度以苯妥英为内标,测定苯妥英的血药浓度以卡马西平为内标,流动相:甲醇-水(60:40),柱温40℃,检测波长:210 nm,流速:1.0 mL·min-1.结果:苯巴比妥、苯妥英、茶碱、卡马西平分别在2.5～40 mg·L-1,2.5～40mg·L-1,2.5～40 mg·L-1,1.25～40 mg·L-1范围内的线性关系良好,日内和日间RSD＜10%(n=5).结论:该方法具有良好的准确性、精密性和较高的灵敏度,且简便、快速、稳定,适用于苯巴比妥、苯妥英、卡马西平、茶碱治疗药物血药浓度监测.     

HPLC法同时测定5种抗癫痫药的血清药物浓度

目的建立同时测定拉莫三嗪、苯巴比妥、苯妥英、卡马西平和氯硝西泮血清浓度的HPLC法。方法血清样品经甲醇沉淀蛋白后直接进样分析,色谱柱为Waters C18(5μm,4.6×250mm)柱,流动相为甲醇-水(55∶45),检测波长235nm。结果在一定浓度范围内(拉莫三嗪:1.3~50.0μg/m L;苯巴比妥:2.5~100.0μg/m L;苯妥英:2.2~70.0μg/m L;卡马西平:1.8~35.0μg/m L;氯硝西泮:2.5~80.0μg/m L),各药物的峰面积与浓度呈良好的线性关系。低、中、高浓度的质控样品回收率均高于95%,相对标准差(RSD)均小于10%。结论本方法操作简便,结果稳定可靠,适用于临床进行血药浓度监测。     

高压液相色谱法同时快速测定苯巴比妥、苯妥英、卡马西平的血药浓度

本文报导了采用高效液相色谱法同时测定苯巴比妥、苯妥英、卡马西平三种药物的血药浓度的方法,本方法具有快速、简捷、干扰能力强等特点.三种药品的保留时间分别为:苯巴比妥2.16min、苯妥英3.56min、卡马西平4.08min;回收率94～109%,日间差异(CV%)0.85～2.93%,日内差异(CV%)0.63～3.14%.     

苯巴比妥和苯妥英钠及卡马西平血药浓度测定

目的：建立一种简便可行的反相高效液相色谱法(RP HPLC)，一步同时测定苯巴比妥、苯妥英钠、卡马西平的血药浓度。方法：患者血清经二氯甲烷提取后在C18柱上分析，流动相为甲醇∶水(57∶43)，柱温30℃，紫外检测波长254 nm，流速0.8 mL·min 1。结果：线性范围分别为2.5～40，2.5～40，1.25～20 μg·mL 1，日内和日间RSD均小于10.0%(n＝5)。结论：该法简便、稳定，用于苯巴比妥、苯妥英钠、卡马西平的血药浓度监测，效果良好。     

HPLC法测定血清中苯巴比妥和卡马西平的浓度

目的建立人血清中苯巴比妥、卡马西平浓度的高效液相色谱含量测定方法。方法采用ODS-Hypersil(4.6 mm×100 mm,5μm)色谱柱,以甲醇∶水(55∶45)为流动相,紫外检测波长为254nm,以苯妥英为内标。结果苯巴比妥在2.5~40μg.mL-1浓度范围内线性关系良好(r=0.9996),平均回收率为100.69%,RSD为1.8%;卡马西平在1.25~20μg.mL-1浓度范围内线性关系良好(r=0.9995),平均回收率为98.67%,RSD为2.1%。日内和日间RSD均不大于3%。结论本方法准确、快速、简便,可作为苯巴比妥和卡马西平血药浓度监测的常规方法。     

高效液相色谱法测定血清中苯巴比妥、苯妥英、卡马西平、氯硝基安定的浓度

目的：建立血清中苯巴比妥（PB）、苯妥英（PT）、卡马西平（CBZ）、氯硝基安定（CNZP）浓度测定的高效液相色谱。方法：以PB、PT互为内标，ODS-Hypersil柱为分析柱，甲醇-水-β-环糊精（45：55：0.01)为流动相；流速为0.8ml/min，紫外检测波长254nm。结果：PB、PT、CBZ、CNZP分离良好，最低检测浓度分别为0.25,0.5,0.05,0.015μg/ml；线性范围分别为2.5-40,2.5-40,1.25-20,0.02-0.32μg/ml；相对回收率分别为97.8%,102.1%,102.3%,103.3%；日蚋、日间RSD均小于10%。结论：该法操作简便，结果可靠，适用于临床开展药物浓度监测。     

HPLC法同时测定血清中苯巴比妥、苯妥英和卡马西平的浓度

目的 :建立快速测定血清中苯巴比妥、苯妥英和卡马西平浓度的方法。方法 :色谱柱DiamonsilC18(4 .6mm× 2 5 0mm ,5 μm) ,流动相甲醇∶水∶乙腈 (4 0∶4 5∶15 ) ,流速1.2ml·min-1,检测波长 2 4 0nm ,内标硝西泮 ,柱温 4 0℃。结果 :提取回收率为 84 .4～ 89.2 % ,日内和日间RSD均 <7.9% ;标准曲线相关性良好。对 10 4例患者作血清浓度监测 ,临床效果满意。结论 :本方法可作为苯巴比妥、苯妥英和卡马西平的血药浓度监测的常规方法。     

反相高效液相色谱法测定苯巴比妥血药浓度

目的:建立一种快速测定苯巴比妥血药浓度的方法.方法:采用反相高效液相色谱法,以卡马西平为内标,测定苯巴比妥协药浓度.色谱柱shimadzu Shimpack CLC-C_(18)不锈钢柱,流动相为甲醇一水(60:40),流速0.8ml/min,检测波长254nm.结果:在5~40μg/ml浓度范围内线性良好(r=0.9999),最低检测限为11.57ng/ml高、中、低三种浓度的平均回收率分别为100.24%,100.28%,99.41%,RSD分别为0.7%,2.7%,5.8%(n=9).日内和日间平均RSD分别为3.3%,5.2%,8.7%和7.3%,7.3%,9.2%(n=9).结论:该方法准确、快速、简便,灵敏度高,重现性好,可作为苯巴比妥血药浓度监测的常规方法.     

超高效液相色谱法测定血清中苯妥英钠、苯巴比妥和卡马西平的浓度

目的建立超高效液相色谱(UPLC)法测定血清中苯妥英钠、苯巴比妥和卡马西平的浓度。方法血清样品经乙腈沉淀蛋白后进样分析。色谱柱为ACQUITY UPLC BEH C18色谱柱,流动相为乙腈-水(28∶72),流速:0.3m L·min-1,检测波长220 nm,柱温20℃。结果苯妥英钠、苯巴比妥和卡马西平的血清浓度分别在2.5~80.0,5.0~160.0,1.0~32.0μg·m L-1线性关系良好,日内、日间精密度(RSD)均小于7.28%,提取回收率为96.18%~103.89%。结论本方法简便、快速、准确,可用于测定血清中苯妥英钠、苯巴比妥和卡马西平的浓度。     

高压液相色谱法同时快速测定苯巴比妥、苯妥英、卡马西平的血药浓度

本文报导了采用高效液相色谱法同时剂定苯巴比妥、苯妥英，卡马西平三种药物的血药浓度的方法，本方法具有快速、简捷、干扰能力强等特点。三种药品的保留时间分别为：苯巴出妥2．16min、苯妥英3.56min、卡马西平4.08min；回收率94～109％，日间差异(CV％)0．85～2．93％，日内差异(CV％)0．63～3．14％。     

高效液相色谱法测定苯巴比妥、苯妥英、卡马西平的血药浓度

目的 :建立 HPL C法测定抗癫药苯巴比妥 (PB)、苯妥英 (PT)、卡马西平 (CBZ)的血药浓度。方法 :反相柱 ODS- Hy-persil(4.6 m m× 10 0 mm ,5︼m ) ,流动相为甲醇∶水 (5 2∶ 48) ,流速 0 .8m l/ m in,紫外检测波长 2 5 4nm ,以上 3药互为内标。标本经 CH2 Cl2 提取 ,蒸干后用流动相重溶进样。结果 :PB、PT、CBZ的保留时间分别为 3.2 2、5 .5 7、6 .80 m in;最低检测浓度分别为 0 .2 5、0 .5、0 .0 5︼g/ m l;线性范围分别为 2 .5～ 40、2 .5～ 40、1.2 5～ 2 0︼g/ ml;相对回收率分别为 10 1.49%、10 4.19%、98.70 % ;日内 RSD分别为 1.81%、5 .94%、1.81% ;日间 RSD分别为 6 .0 6 %、3.35 %、3.96 %。结论 :本法具快速、灵敏、实用等优点。     

Evaluation of therapeutic drug level monitoring of phenobarbital, phenytoin and carbamazepine in Iranian epileptic patients

OBJECTIVE: The antiepileptic drugs phenobarbital, phenytoin and carbamazepine are widely used for the treatment of partial and tonic-clonic seizures. Large inter-individual differences in pharmacokinetics of these drugs, and the intermittent nature of epileptic attacks, increase the need for therapeutic drug level monitoring of these drugs. MATERIAL AND METHODS: In this study, data from the therapeutic drug monitoring of phenobarbital, carbamazepine and phenytoin in 328 epileptic patients were evaluated. Serum levels of drugs were determined in a University Department of Pharmacology by high-performance liquid chromatography. RESULTS: In this study, approximately 56% of patients were treated with 1; 30% with 2; and 14% with 3 antiepileptic drugs. In patients receiving 1 antiepileptic drug, the percentages treated with phenobarbital, carbamazepine and phenytoin were 41, 38 and 21%, respectively. In patients who received carbamazepine, serum levels in 40% of the patients were in the range of 4-8 microg/ml and more than in the range 4-12 microg/ml in 74% of the patients. In phenobarbital-treated patients, serum levels in 73% of the patients were in therapeutic range of 10-40 microg/ml, and about 44% of phenytoin-treated patients had serum levels in therapeutic range of 10-20 microg/ml. Approximately 50% of carbamazepine- and phenytoin-treated patients and approximately 70% of phenobarbital-treated patients were completely controlled. The frequency of concentrations within the therapeutic ranges decreased in patients using more than 1 antiepileptic drug. In patients who received both phenobarbital and sodium valproate, serum levels of phenobarbital were significantly (p < 0.05) greater than in patients who were taking this drug in combination with carbamazepine or phenytoin. CONCLUSION: Our results indicate that serum levels of antiepileptic drugs, and the percentage of patients with complete seizure control are comparable with results obtained in other populations in previous studies.     

反相高效液相色谱法同时测定茶碱和3种抗癫痫药血药浓度

目的建立可同时测定茶碱和苯巴比妥、苯妥英钠、卡马西平血药浓度的反相高效液相色谱法。方法色谱柱为Promosil C18柱(150 mm×4.6 mm,5μm),流动相为甲醇-水(60∶40),检测波长205 nm,流速0.7 mL/min,柱温25℃。结果该色谱条件下,茶碱、苯巴比妥、苯妥英钠、卡马西平分离良好,血药浓度线性范围茶碱为0.30～180.00μg/mL(r=0.999 7),苯巴比妥为0.42～169.60μg/mL(r=0.999 9),苯妥英钠为0.40～170.00μg/mL(r=0.999 2),卡马西平为0.20～140.00μg/mL(r=0999 8),平均回收率分别是97.3%,98.0%,103.1%,99.3%,日内及日间精密度RSD均小于6%。结论该方法操作简便、快速、准确,4种药物互不干扰,可用于临床血药浓度监测。     

反相高效液相色谱法同时测定苯妥英钠、卡马西平的血药浓度

目的建立反相高效液相色谱法同时测定苯妥英钠、卡马西平的血药浓度。方法采用C18柱（200mm×4．6mm，5μm），甲醇-水（48：52）为流动相，紫外检测波长为205nm，流速1．1mL／min，柱温40℃。结果两种药物分离良好，苯妥英钠、卡马西平质量浓度线性范围分别为2．14～42．8μg／mL和2．04～20．40μg／mL，方法回收率分别为99．33％和99．64％，提取回收率分别为97，13％和96．64％，日内、日间RSD均小于4％．结论该方法操作简便、快速、准确，可用于临床治疗药物的监测。     

HPLC法同时测定血清中苯巴比妥、苯妥英和卡马西平的浓度

采用 ＲＰ－ＨＰＬＣ法,以甲醇：乙腈：水（４０： ８： ５２）为流动相,检测波长２５４ｎｍ,采用外标法同时测定血清中苯巴比妥、苯妥英和卡巴西平浓度。结果苯巴比妥、苯妥英和卡马西平浓度分别在３．９７～７９．４２μｇ／ｍｌ,２．０１～８０．２４μｇ／ｍｌ, １． ０２～４０．９μｇ／ｍｌ浓度范围内呈线性关系。     

反相高效液相色谱外标法测定卡马西平和茶碱的血药浓度

目的建立测定卡马西平与茶碱血药浓度的反相高效液相色谱外标法。方法以二氯甲烷为萃取溶剂,采用外标法进行含量测定。色谱柱为XDB C18柱(150 mm×4.6 mm,5.0μm),流动相为甲醇-水(60∶40),流速为0.7 mL/min,检测波长为235 nm。结果卡马西平与茶碱的质量浓度线性范围分别为1.25～20μg/mL和2.5～40μg/mL,平均回收率分别为102.0%和101.4%,日内、日间精密度的RSD均小于5%。结论该法测定卡马西平与茶碱的血药浓度准确、简便、经济,适合于临床应用。     

HPLC法同时测定2种茶碱类和3种抗癫痫药的血药浓度

目的建立可同时测定人血清中茶碱、多索茶碱、苯巴比妥、苯妥英钠及卡马西平浓度的HPLC方法。方法色谱柱：XTerra C18（150mm×4．6mm,3．5μm）;流动相：甲醇-水（54：46）;流速0．7mL·min^-1;检测波长205nm;柱温40℃;内标：艾司唑仑。血清样品经3g·L^-1 ZnSO4的甲醇溶液处理后,取20μL直接进样测定。结果茶碱、多索茶碱、苯巴比妥、苯妥英钠及卡马西平分别在质量浓度0．79～101、0．78～100、1．59～204、0．79～101．5、0．47～60mg·L^-1内呈线性关系（r〉0．99）,方法日内、日间回收率均为85％～115％,RSD≤13．45％。结论本次建立的同时测定人血清中2种茶碱类与3种抗癫痫药物的HPLC法简便、准确、精密、专属性强,可应用于这类药物的常规血药浓度监测。     

Validated high performance liquid chromatographic method for simultaneous determination of phenytoin, phenobarbital and carbamazepine in human serum

A high performance liquid chromatographic (HPLC) method for the simultaneous determination of phenytoin (CAS 57-41-0), phenobarbital (CAS 50-06-6, phenobarbitone) and carbamazepine (CAS 298-46-4) is described. The serum was extracted with ethyl acetate, the dried extract was reconstituted in mobile phase and the aliquot was injected. The eluent drugs were detected at 230 nm. The mobile phase consisting of methanol: water: glacial acetic acid mixture (67:33:1, v/v/v) was used at a flow rate of 1 ml/min on C-18 column. The absolute recovery was above 96% of all the three drugs over a concentration range of 0.5-50.0 micrograms/ml. The inter-day and intra-day precision relative standard deviation (RSD) ranged from 0.79-5.13% and 0.11-6.81%, respectively. The method is simple, rapid, accurate and sensitive and is presently used for therapeutic drug monitoring in epileptic patients. The results obtained with this method showed very good clinical correlation.     

高效液相色谱法同时测定人血清中氨茶碱、苯巴比妥、苯妥英钠及卡马西平的浓度

目的：建立同时测定人血清中氨茶碱（APL）、苯巴比妥（PB）、苯妥英钠（DPH）和卡马西平（CBZ）的高效液相色谱（HPLC）法。方法：以Agilent TC-C18（250 mm×4.6 mm,5μm）为分析柱,甲醇-水（60∶40）为流动相,检测波长230 nm,流速1.0 ml/min,柱温35℃。结果：APL、PB、DPH、CBZ均能达到良好的分离,与相邻峰的分离度（R）均〉1.5;线性范围分别为1.01～40.34 mg/L（r=0.999 5）、1.24～59.52 mg/L（r=0.999 1）、2.60～31.20 mg/L（r=0.998 6）、1.09～32.61 mg/L（r=0.999 2）;平均回收率分别为98.15%、99.25%、98.86%、100.3%;日内和日间精密度的RSD均〈4.3%。结论：本法灵敏、准确、简便、快速,适用于临床血药浓度的检测。     

Quantification of carbamazepine, carbamazepine-10,11-epoxide, phenytoin and phenobarbital in plasma samples by stir bar-sorptive extraction and liquid chromatography

A sensitive and reproducible stir bar-sorptive extraction and high-performance liquid chromatography-UV detection (SBSE/HPLC-UV) method for therapeutic drug monitoring of carbamazepine, carbamazepine-10,11-epoxide, phenytoin and phenobarbital in plasma samples is described and compared with a liquid:liquid extraction (LLE/HPLC-UV) method. Important factors in the optimization of SBSE efficiency such as pH, extraction time and desorption conditions (solvents, mode magnetic stir, mode ultrasonic stir, time and number of steps) assured recoveries ranging from 72 to 86%, except for phenytoin (62%). Separation was obtained using a reverse phase C(18) column with UV detection (210nm). The mobile phase consisted of water:acetonitrile (78:22, v/v). The SBSE/HPLC-UV method was linear over a working range of 0.08-40.0mugmL(-1) for carbamazepine, carbamazepine-10,11-epoxide and phenobarbital and 0.125-40.0mugmL(-1) for phenytoin, The intra-assay and inter-assay precision and accuracy were studied at three concentrations (1.0, 4.0 and 20.0mugmL(-1)). The intra-assay coefficients of variation (CVs) for all compounds were less than 8.8% and all inter-CVs were less than 10%. Limits of quantification were 0.08mugmL(-1) for carbamazepine, carbamazepine-10,11-epoxide and phenobarbital and 0.125mugmL(-1) for phenytoin. No interference of the drugs normally associated with antiepileptic drugs was observed. Based on figures of merit results, the SBSE/HPLC-UV proved adequate for antiepileptic drugs analyses from therapeutic levels. This method was successfully applied to the analysis of real samples and was as effective as the LLE/HPLC-UV method.