CAJ | 학술논문

本文建立了一种快速、高灵敏的HPLC-MS/MS法用于检测人血浆中的草乌甲素浓度.血浆样品采用沃特斯HLB小柱进行固相萃取,汉邦C18色谱柱(150mm×4.6 mm,5μ m)进行分离,流动相为甲醇∶水(85∶15,v/v),水相含10 mmol/L的醋酸铵和0.1％的甲酸.采用ESI源和多反应监测(MRM)的方式进行检测,草乌甲素及内标的反应离子对分别为644.4/584.4和237.2/194.2,草乌甲素血药浓度在0.010～1.0 ng/mL范围内线性关系良好,最低定量限为0.010 ng/mL可以满足口服0.4mg草乌甲素后血药浓度的检测,日内日间及质控样品精密度及准确度均在允许范围内.本检测方法被成功的应用在中国健康志愿者生物等效性研究中,20名志愿者口服0.4mg草乌甲素试验制剂和参比制剂后主要药代动力学参数分别如下:Cmax(0.325±0.110),(0.323±0.115) ng/mL;AUC0-16(1.627 ±0.489),(1.732±0.556) ng ·h/mL;AUC0-∞ (1.730±0.498),(1.831±0.562)ng·h/mL;t1/2(4.26±0.95),(3.80±0.90) h;Tmax(1.34±0.54),(1.83±0.99) h.
본문건립료일충쾌속、고령민적HPLC-MS/MS법용우검측인혈장중적초오갑소농도.혈장양품채용옥특사HLB소주진행고상췌취,한방C18색보주(150mm×4.6 mm,5μ m)진행분리,류동상위갑순∶수(85∶15,v/v),수상함10 mmol/L적작산안화0.1％적갑산.채용ESI원화다반응감측(MRM)적방식진행검측,초오갑소급내표적반응리자대분별위644.4/584.4화237.2/194.2,초오갑소혈약농도재0.010～1.0 ng/mL범위내선성관계량호,최저정량한위0.010 ng/mL가이만족구복0.4mg초오갑소후혈약농도적검측,일내일간급질공양품정밀도급준학도균재윤허범위내.본검측방법피성공적응용재중국건강지원자생물등효성연구중,20명지원자구복0.4mg초오갑소시험제제화삼비제제후주요약대동역학삼수분별여하:Cmax(0.325±0.110),(0.323±0.115) ng/mL;AUC0-16(1.627 ±0.489),(1.732±0.556) ng ·h/mL;AUC0-∞ (1.730±0.498),(1.831±0.562)ng·h/mL;t1/2(4.26±0.95),(3.80±0.90) h;Tmax(1.34±0.54),(1.83±0.99) h.
A high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESIMS/MS) method was developed and validated for the determination of Bulleyaconitine A (BLA) in human plasma using carbamazepinum as internal standard (IS).Plasma samples were extracted with Waters Oasis HLB solid-phase cartridges,separated on a reversed C18 column (150 mm × 4.6 mm,5 μm) with a mobile phase of methonal - 10 mmol/L ammonium acetate solution containing 0.1％ formic acid (85:15,v/v).Bulleyaconitine A and IS were detected in the multiple reaction monitoring mode (MRM) with precursor to product ion transitions of m/z644.4/584.4 and 237.2/ 194.2,respectively.The method exhibited a linear range of 0.010-1.0 ng/mL for BLA in human plasma.The lowest limit of quantification (LLOQ) was 0.010 ng/mL,which was sensitive enough for the pharmacokinetic study of BLA.Acceptable precision and accuracy were obtained for concentrations of the calibration standard and the quality control (QC).The validated method was successfully applied for evaluation of a bioequivalence study in Chinese healthy volunteers.The main pharmacokinetics parameters after oral administration of 0.4 mg BLA test or reference formulation were as follows:Cmax (0.325 ± 0.110),(0.323 ± 0.115 ) ng/mL;AUC0-16 ( 1.627 ± 0.489),( 1.732 ± 0.556) ng · h/mL;AUC0-∞ (1.730 ±0.498),(1.831 ±0.562) ng · h/mL;t1/2 (4.26 ±0.95),(3.80 ±0.90) h;Tmax (1.34 ±0.54),(1.83±0.99) h.