摘要
目的:建立同时测定人血浆中奥氮平、利培酮和帕潘立酮浓度的方法。方法:血浆样品经液-液萃取后,以盐酸丁螺环酮为内标,采用超高效液相色谱-串联质谱法测定。色谱柱为ACQUITY UPLCTM BEH C_(18),流动相为甲醇-0.01 mol/L甲酸铵水溶液,梯度洗脱,流速为0.2 mL/min,柱温为45℃,进样量为5μL。采用电喷雾离子源,以多反应监测模式进行正离子扫描,用于定量分析的离子对分别为m/z 313.29→256.25(奥氮平)、m/z 411.42→191.19(利培酮)、m/z 427.45→207.18(帕潘立酮)和m/z 386.43→122.37(内标)。结果:奥氮平、利培酮、帕潘立酮血药浓度分别在0.426~108.954、0.213~54.476、0.213~54.476 ng/mL范围内线性关系良好;日内、日间RSD<20%,方法回收率分别为83.3%~112.9%,90.0%~109.8%和95.2%~114.9%,提取回收率分别为65.5%~95.0%、73.9%~98.5%和73.6%~99.4%,基质效应和稀释效应均不影响待测物血药浓度的测定。采用该法测得100例精神分裂症患者奥氮平、利培酮和帕潘立酮的血药浓度分别为(103.3±73.6)、(13.1±13.1)和(23.2±20.0)ng/mL。结论:该方法简单、快速、灵敏、特异性高,可用于奥氮平、利培酮和帕潘立酮血药浓度测定及药动学研究。
OBJECTIVE： To develop a method for the concentration determination of olanzapine, risperidone and paliperidone in human plasma. METHODS： After liquid-liquid extraction, using buspirone hydrochloride as internal standard, the concentration of plasma sample was determined by UPLC-MS/MS. The determination was performed on ACQUITY UPLCTM BEH C18 column with mobile phase consisted of methanol-0.01 mol/L ammonium formate solution （gradient elution） at flow rate of 0.2 mL/min. The column temperature was 45 ℃, and sample size was 5 μL. The electrospray ionization source was adopted for positive ion scanning under MRM mode. Ion-pairs for quantitative analysis were as follows： m/z 313.29→256.25 （olanzapine）, m/z 411.42→191.19 （risperidone）, m/z 427.45→207.18 （paliperidone） and m/z 386.43→122.37 （internal standard）. RESULTS： The linear ranges of olanzapine, risperidone and paliperidone were 0.426-108.954, 0.213-54.476, 0.213-54.476 ng/mL, respectively. RSDs of inter-day and intra-day were all lower than 20%. The recoveries of them ranged 83.3%-112.9%, 90.0%-109.8% and 95.2%-114.9%, respectively. Extraction recoveries ranged 65.5%-95.0%, 73.9%-98.5% and 73.6%-99.4%, respectively. Both plasma matrix effect and dilute effect didn＇t influence the determination of plasma concentration. The plasma concentrations of olanzapine, risperidone and paliperidone in 100 schizophrenia patients were （103.3 ± 73.6）, （13.1 ± 13.1） and （23.2 ± 20.0） ng/mL, respectively. CONCLUSIONS： The method is simple, rapid, sensitive and specific. It can be used for the determination of plasma concentration and pharmacodynamic study of olanzapine, risperidone and paliperidone.
出处
《中国药房》
CAS
北大核心
2017年第8期1045-1048,共4页
China Pharmacy
