CAJ | 학술논문

目的：建立灵敏、专一的测定大鼠血浆中 B7011含量的液相色谱质谱联用仪（LC-mS/ mS）检测方法。方法采用甲醇沉淀蛋白质的方法对血浆样品进行前处理，对方法的线性范围、批内和批间精密度、特异性、基质效应、回收率、准确度和稳定性等指标进行确证，并检测了 SD 大鼠单次静脉注射 B70110.5 mg·kg-1的血药浓度。结果血浆 B7011在30~20000μg·L-1浓度范围内线性良好，定量下限为30μg·L-1；B701160，1000，16000和10000μg·L-1血浆浓度测定的批内精密度分别为5.61%~13.31%，2.31%~8.35%，2.02%~9.47%和4.0%~15.0%，批间精密度分别为10.05%，2.55%，3.75%和8.58%；B701160，1000和16000μg·L-1的回收率为114.12%，109.2%和101.06%；浓度为200，1000，10000和100000μg·L-1的 B7011血浆标品在4℃放置4 h 和-20℃冻存10 d（期间反复冻融3次）的条件下存放稳定。静脉注射 B7011在雌雄大鼠的主要动力学参数：峰浓度分别为8373.28和8564.59μg·L-1；曲线下面积分别为98400和104000μg·L-1·h；消除半衰期分别为41.7和63.6 h。结论建立了大鼠血浆中B7011含量测定的 LC-mS/ mS 方法，能够满足其药代动力学和毒代动力学研究的需要。
목적：건립령민、전일적측정대서혈장중 B7011함량적액상색보질보련용의（LC-mS/ mS）검측방법。방법채용갑순침정단백질적방법대혈장양품진행전처리，대방법적선성범위、비내화비간정밀도、특이성、기질효응、회수솔、준학도화은정성등지표진행학증，병검측료 SD 대서단차정맥주사 B70110.5 mg·kg-1적혈약농도。결과혈장 B7011재30~20000μg·L-1농도범위내선성량호，정량하한위30μg·L-1；B701160，1000，16000화10000μg·L-1혈장농도측정적비내정밀도분별위5.61%~13.31%，2.31%~8.35%，2.02%~9.47%화4.0%~15.0%，비간정밀도분별위10.05%，2.55%，3.75%화8.58%；B701160，1000화16000μg·L-1적회수솔위114.12%，109.2%화101.06%；농도위200，1000，10000화100000μg·L-1적 B7011혈장표품재4℃방치4 h 화-20℃동존10 d（기간반복동융3차）적조건하존방은정。정맥주사 B7011재자웅대서적주요동역학삼수：봉농도분별위8373.28화8564.59μg·L-1；곡선하면적분별위98400화104000μg·L-1·h；소제반쇠기분별위41.7화63.6 h。결론건립료대서혈장중B7011함량측정적 LC-mS/ mS 방법，능구만족기약대동역학화독대동역학연구적수요。
OBJECTlVE To estabIish a simpIe,sensitive and quick method for determination of B7011 in rat pIasma. METHODS The method of protein precipitation with methanoI was used for pre-treatment of pIasma sampIes determined by Iiquid chromatography mass spectrometer. The Iinear reIa-tionship,intra-batch and inter-batch precision,specificity,matrix effect,recovery rate,the accuracy and stabiIity of the pIasma sampIes were vaIidated. The concentration of B7011 in pIasma was determined by LC-mS/ mS foIIowing a singIe intravenous injection of B7011 0.5 mg·kg-1 to rats. RESULTS The Iinear range of B7011 was 30-20 000 μg·L-1 ,the Iower Iimit of quantification was 30 μg·L-1 in pIasma,the in-tra-batch precision of 60,1000,16 000 and 10 000 ng·mL-1 was 5.61% -13.31%,2.31% -8.35%, 2.02%-9.47% and 4.0%-15.0% respectiveIy,and inter-batch precision was 10.05%,2.55%,3.75% and 8.58% respectiveIy. The recovery of 60,1000,and 16 000 μg·L-1 was 114.12%,109.2% and 101.06%respectiveIy. The average peak concentrations were 8373.28 and 8564.59 μg·L-1 ,the mean AUC was 98 400 and 104 000 μg·L-1·h and the t1/ 2z for B7011 was 41.7 and 63.6 h in bIood of maIe and femaIe rats, respectiveIy. CONCLUSlON The estabIished method is sensitive, fast and simpIe and concentration of B7011 in pIasma is determined by LC-mS/ mS foIIowing a singIe intravenous injection of B7011 0.5 mg·kg-1 to rats. It can satisfy the requirements of pharmacokinetic and toxicokinetic studies.