CAJ | 학술논문

建立并评价了一种简单灵敏的方法测定狗血浆中PZS的含量.该方法利用HPLC-FLD结合乙醚萃取的前处理方法,采用C18色谱柱(150 mm×4.6 mm,5 μm),流动相为30％乙腈和70％乙酸-乙酸钠缓冲液(pH=3.6),荧光检测器的激发波长为258 nm,发射波长为387 nm,在流动相流速为1.0 mL/min时,其PZS和内标物的保留时间分别为4.4和5.8 min.标准曲线在1.0～1000.0 ng/mL的浓度范围内呈线性相关(r2＞0.998),检出限为0.4 ng/mL,标准曲线的日间变异系数低于5.0％,准确度在92.7％～104.2％范围内.在3 d的分析质量控制研究中,日内和日间精密度均小于10％,准确度为95.9％～112.7％.该方法成功应用于一种新的口服制剂(PZS-磺丁基醚-β-环糊精包合物)的临床前期药代动力学评价,结果表明:该新型的包合药物具有缓释PZS的功效,且其相对生物利用率为105.0％.
건립병평개료일충간단령민적방법측정구혈장중PZS적함량.해방법이용HPLC-FLD결합을미췌취적전처리방법,채용C18색보주(150 mm×4.6 mm,5 μm),류동상위30％을정화70％을산-을산납완충액(pH=3.6),형광검측기적격발파장위258 nm,발사파장위387 nm,재류동상류속위1.0 mL/min시,기PZS화내표물적보류시간분별위4.4화5.8 min.표준곡선재1.0～1000.0 ng/mL적농도범위내정선성상관(r2＞0.998),검출한위0.4 ng/mL,표준곡선적일간변이계수저우5.0％,준학도재92.7％～104.2％범위내.재3 d적분석질량공제연구중,일내화일간정밀도균소우10％,준학도위95.9％～112.7％.해방법성공응용우일충신적구복제제(PZS-광정기미-β-배호정포합물)적림상전기약대동역학평개,결과표명:해신형적포합약물구유완석PZS적공효,차기상대생물이용솔위105.0％.
A simple and sensitive high performance liquid chromatography method using fluorescence detection (HPLCFLD) and a one-step single solvent extraction for the determination of prazosin(PZS) in dog plasma is developed and validated. After extraction with ether, the chromatographic separation of PZS is carried out using a reverse phase C18 column (150 mm ×4.6 mm, 5 μm) with a mobile phase of 30％ acetonitrile and 70％ acetic acid-sodium acetate buffer solution (pH = 3.6) and quantified by fluorescence detection operated with an excitation wavelength of 258 nm and an emission wavelength of 387 nm. The flow rate of the mobile phase is 1.0 mL/min and the retention time of PZS and the internal standard is found to be 4. 4 and 5. 8 min, respectively. The calibration curve is linear within a concentration range from 1.0 to 1 000.0 ng/mL (r2 ＞ 0. 998). The limit of detection is 0.4 ng/mL. The inter-day coefficient of variation (COV) of the calibration standards is below 5.0％ and the mean accuracy is in the range from 92. 7％ to 104. 2％. Moreover, by analyzing quality control plasma samples for three days, the results show that the method is precise and accurate, for the intra- and interday COV within 10％ and the accuracy from 95.9％ to 112.7％.The developed and validated method is successfully applied to pharmacokinetic study for the preclinical evaluation of a new peroral PZS-sulfobutyl ether beta-cyclodextrin (PZS-SBE-β-CD)inclusion complex tablets (test preparation), which demonstrates that the test preparation released PZS is conducted in a slow and controlled way, and the relative bioavailability of the test preparation is found to be 105.0％.