摘要
目的:建立液相色谱-串联质谱法(HPLC-MS-MS)测定人血浆中芬太尼的浓度。方法:以D5-芬太尼为内标,采用正己烷处理血浆样品。色谱柱为Thermo Hypurity C18(150mm×2.1mm,5μm),流动相为甲醇∶水(含0.1%甲酸)=(85∶15,V/V),流速为0.3mL/min,柱温40℃;质谱条件为电喷雾电离源(ESI),检测方式为正离子方式、多离子反应监测(MRM),用于定量分析的离子为芬太尼m/z 337.1→188.1,D5-芬太尼m/z 341.9→187.9。结果:芬太尼血药浓度在19.53～5000pg/mL范围内线性关系良好,定量下限为19.53pg/mL,日内和日间变异均小于5.16%,提取回收率均在90%以上;应用此方法研究了24名健康男性受试者使用两种芬太尼透皮贴剂的药代动力学特点,受试制剂对参比制剂的相对生物利用度为(94.0±19.5)%。结论:本法具有快速、简便、灵敏、准确等特点,适合人血浆中芬太尼浓度测定。两种制剂生物等效。
AIM： To establish an HPLC-MS/ MS assay to determine fentanyl in human plas- ma. METHODS： D-fentanyl was used as an in- teral standard. Human plasma samples were extracted by n-hexane. The separation was carried out on an Thermo Hypurity C18 （150 mm× 2.1 ram, 5 μm） column at 40 ℃. The mobile phase consisted of methanol--0.1% formic acid （85 ：15, V/V） at a flow rate of 0. 3 mL/min. Elec- trospray ionization （ESI） source was applied and operated in the positive ion mode. Quantitaion was performed using multiple reaction monito- ring （MRM） of the m/z 337.1→188.1 for fenta- nyl , and m/z 341.9→187.9 for D-fentanyl. RE- SULTS= The liner calibration curves were ob- tained in the range of 19.53--5000 pg/mL for fentanyl. The lower limit of quantification was 19.53 pg/mL. The relative standard deviation of the intra-assay and inter-assay precision of varia- tion was less than 5.160%. The extraction recov- ery for fentanyl was above 90%. To study the pharmacokinetics of two transdermal patches of fentanyl, preparations were given to 24 healthy volunteers, and the relative bioavailability of AUG0-144 was （94.0±19.5）%. CONCLUSION： It is an accurate, sensitive and rapid method that can be applied to determine fentanyl in human plasma. Two preparations of fentanyl are bio- equivalent.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2012年第7期785-790,共6页
Chinese Journal of Clinical Pharmacology and Therapeutics
