高效液相色谱串联质谱法同时测定人血浆中加巴喷丁和普瑞巴林浓度  

Simultaneous Determination of Gabapentin and Pregabalin in Human Plasma by HPLC-MS/MS

作　　者：李银洛 唐才林 盛长城[2] 陈宇 龙兴震 白雪 LI Yinluo;TANG Cailin;SHENG Changcheng;CHEN Yu;LONG Xingzhen;BAI Xue(Guizhou University of Traditional Chinese Medicine,Guiyang,Guizhou,China 550002;Guizhou Provincial People's Hospital,Guiyang,Guizhou,China 550002;The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang,Guizhou,China 550002)

机构地区：[1]贵州中医药大学,贵州贵阳550002 [2]贵州省人民医院,贵州贵阳550002 [3]贵州中医药大学第一附属医院,贵州贵阳550002

出　　处：《中国药业》2023年第23期67-71,共5页China Pharmaceuticals

基　　金：贵州省人民医院青年基金项目[GZSYQN〔2017〕14号];贵州省人民医院2019年度国家自然科学基金后补助资金项目[GPPH-NSFC-2019-17,〔2019〕GPPH-NSFC-D-2019-25]。

摘　　要：目的建立同时测定人血浆中加巴喷丁(GBP)和普瑞巴林(PGB)浓度的高效液相色谱串联质谱法。方法样品经甲醇沉淀蛋白后,以茶碱为内标(IS),色谱柱为Phenomenx Luna®Omega C_(18)柱(50 mm×2.1 mm,1.6μm),流动相为0.1%甲酸水溶液-乙腈(梯度洗脱),流速为0.30 mL/min,柱温为30℃,进样量为1μL。采用电喷雾离子源,正离子模式下进行多反应监测,用于定量分析的离子对质荷比(m/z)分别为172.00→154.10(GBP)、160.00→55.10(PGB)、181.10→124.00(IS)。结果GBP和PGB质量浓度均在100.00~12800.00 ng/mL范围内与峰面积线性关系良好(r=0.9992,0.9996,n=9),定量下限为100.00 ng/mL,日间、日内精密度试验结果的RSD均小于20%(n=6),稳定性试验的RSD均小于15%,提取回收率分别为93.89%~101.55%和94.38%~101.93%,基质效应分别为88.76%~100.95%和91.87%~102.08%。20例服药患者经剂量校正后,GBP和PGB稳态血药浓度分别在2268.68~13652.27 ng/(mL·g)和11987.27~36513.73 ng/(mL·g)范围内。结论该方法稳定快速、灵敏度高,血浆消耗量少,可用于带状疱疹后神经痛患者服药后血药浓度监测及药代动力学研究。Objective To establish a high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method for the simultaneous determination of gabapentin and pregabalin in human plasma.Methods The sample was pretreated by the methanol precipitation protein method,and theophylline was taken as the internal standard(IS).The chromatographic column was Phenomenex Luna®Omega C_(18) column(50 mm×2.1 mm,1.6μm),the mobile phase was 0.1%formic acid aqueous solution-acetonitrile(gradient elution),the flow rate was 0.30 mL/min,the column temperature was 30℃,and the injection volume was 1μL.The electrospray ionization(ESI)was used to conduct the multi-reaction monitoring mode with positive ion mode scanning.The ion pairs used for quantitative analysis were mass charge ratio(m/z)172.00→154.10(GBP),160.00→55.10(PGB),181.10→124.00(IS),respectively.Results The linear range of gabapentin and pregabalin was 100.00-12800.00 ng/mL(r^(2)=0.9992,0.9996,n=9),and the lower limit of quantification(LOQ)was 100 ng/mL.The RSDs of the intra-day and intra-day precision results were less than 20%(n=6),and the RSD of the stability test was less than 15%.The extraction recovery rates of gabapentin and pregabalin were in the ranges of 93.89%-101.55%and 94.38%-101.93%,respectively.The matrix effects of gabapentin and pregabalin were in the ranges of 88.76%-100.95%and 91.87%-102.08%,respectively.The steady-state blood drug concentrations of GBP and PGB in 20 patients who took the medication after dose correction were in the ranges of 2268.68-13652.27 ng/(mL·g)and 11987.27-36513.73 ng/(mL·g),respectively.Conclusion This method is stable,rapid,highly sensitive,and has low plasma consumption.It can be used for therapeutic drug monitoring and pharmacokinetic research in patients with postherpetic neuralgia after taking medication.

关 键 词：加巴喷丁 普瑞巴林 高效液相色谱串联质谱法 血药浓度 

分 类 号：R969.1[医药卫生—药理学] R971.1[医药卫生—药学]