本文選題：鹽酸奧普力農(nóng) + 高效液相串聯(lián)質(zhì)譜��； 參考：《長春工業(yè)大學(xué)》2014年碩士論文

【摘要】：鹽酸奧普力農(nóng)屬于磷酸二酯酶抑制劑類治療慢性心衰的正性肌力藥物。本文在于建立一種靈敏度高、重現(xiàn)性好、分析時間短、樣品處理簡便,適用于樣品的高通量分析人血漿及尿液中奧普力農(nóng)的高效液相串聯(lián)質(zhì)譜(LC-MS/MS)測定方法,并在該方法的基礎(chǔ)上,對健康受試者靜脈推注奧普力農(nóng)鹽酸鹽后人體藥代動力學(xué)進(jìn)行研究。為奧普力農(nóng)鹽酸鹽推注液提供臨床依據(jù)。 異丙肌苷是一種免疫增強劑。異丙肌苷有三部分肌苷、對乙酰氨基苯甲酸和N,N一二甲氨基-2-丙醇通過合成方法制備而來。服用異丙肌苷后,其在體內(nèi)可以迅速水解為肌苷,本文建立了一種快速、靈敏、準(zhǔn)確的肌苷LC-MS/MS分析方法,并通過該方法測定健康受試者服用異丙肌苷后,血漿中的肌苷含量。 奧普力農(nóng)采用液液萃取吹干上清復(fù)溶后進(jìn)行LC-MS/MS分析。實驗中采用MRM模式,同時檢測奧普力農(nóng)及內(nèi)標(biāo)可待因。并對其各種穩(wěn)定性、提取回收率、基質(zhì)效應(yīng)等進(jìn)行了方法確證,結(jié)果表明此方法符合CFDA的相關(guān)要求。同時選用12名健康受試者,隨機進(jìn)行三劑量三交叉方式進(jìn)行靜脈推注給藥,并于設(shè)定時間點進(jìn)行樣品的采集并保存待分析。 由于肌苷屬于內(nèi)源性物質(zhì),且肌苷在血液中不穩(wěn)定,本文采用特殊沉淀蛋白的方法對其進(jìn)行處理：全血取出后置于肝素化試管中,立即低溫離心。取出血漿置于另一含有高氯酸的試管中,充分振蕩混勻,并低溫離心,取上清,于培80℃冷凍待測。 本論文建立了人血漿及尿液中鹽酸奧普力農(nóng)的LC-MS/MS分析方法,該方法快速、準(zhǔn)確、靈敏,適于奧普力農(nóng)的生物樣品分析。健康人靜脈推注低、中、高三劑量后,其Cmax分別為20.86±12.97(mean±SD)、43.92±22.59和67.25±19.37；t1/2分別為0.96±0.26、0.84±0.37和0.99±0.17；AUC0-∞分別為10.93±3.83、22.55±7.53和37.42±7.70。 本研究建立LC-MS/MS測定人血漿中肌苷濃度的方法并進(jìn)行了方法確證。該方法專屬性強,樣品處理方便,靈敏度高,適用于肌苷臨床藥動學(xué)研究。
[Abstract]:Aupu hydrochloric acid is a positive inotropic drug for the treatment of chronic heart failure with phosphodiesterase inhibitors. This paper is to establish a high throughput analysis method for high throughput analysis of Aupu force farm in human plasma and urine with high sensitivity, good reproducibility, short analysis time, simple sample treatment, and high throughput analysis of LC-MS/MS in human plasma and urine. On the basis of this method, the pharmacokinetics of Aupu in healthy volunteers were studied after intravenous injection of Aupu hydrochloride, which provided a clinical basis for Aupu hydrochloride injection.
Isosinosine is an immunoenhancer. Isosinosine has three parts of inosine, which is prepared by synthesis of acetaminophen and N, N one or two methylamino -2- propanol. After taking isosinosine, it can quickly hydrolyze into inosine in the body. A rapid, sensitive and accurate method for the analysis of inosine LC-MS/MS was established and passed by this method. Methods the inosine content in plasma of healthy subjects after taking isoprenin was determined.
Aupu force farmer uses liquid liquid extraction and blow dry supernatant to carry out LC-MS/MS analysis. In the experiment, MRM model was used, and Aupu force farm and codeine were detected at the same time. All kinds of stability, recovery rate and matrix effect were confirmed by methods. The results showed that this method accords with the requirements of CFDA. At the same time, 12 healthy subjects are selected. Three doses and three crossover methods were randomly administered intravenously, and samples were collected and stored for analysis at set time points.
As inosine is an endogenous substance and inosine is unstable in the blood, this article is treated with a special precipitation protein: after taking out the whole blood and placed in a heparinization test tube, then centrifugation at a low temperature. The plasma is placed in a test tube containing perchloric acid, which is well mixed up and centrifuged at low temperature, Torikami Kiyo, frozen at 80. To be measured.
The method of LC-MS/MS analysis of Aupu hydrochloric acid in human plasma and urine was established in this paper. This method is fast, accurate, sensitive and suitable for the analysis of the biological samples of Aupu. After the low, middle and high dose of healthy human intravenous injection, the Cmax is 20.86 + 12.97 (mean + SD), 43.92 + 22.59 and 67.25 + 19.37 respectively, and t1/2 is 0.96 + 0.26,0.84 + 0.37 respectively. And 0.99 + 0.17; AUC0- infinity were 10.93 + 3.83,22.55 + 7.53 and 37.42 + 7.70. respectively.
In this study, a method for the determination of inosine concentration in human plasma by LC-MS/MS was established and confirmed by method. This method is highly specific, convenient and sensitive. It is suitable for the clinical pharmacokinetic study of inosine.
【學(xué)位授予單位】：長春工業(yè)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：O657.63;R927.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前4條

1 李小明;胡愛虹;;磷酸二酯酶抑制劑的藥理及臨床應(yīng)用進(jìn)展[J];安徽醫(yī)藥;2006年06期

2 劉春玲;王雅君;陳曉虎;;慢性心力衰竭中醫(yī)研究進(jìn)展[J];遼寧中醫(yī)藥大學(xué)學(xué)報;2013年07期

3 鐘大放;以加權(quán)最小二乘法建立生物分析標(biāo)準(zhǔn)曲線的若干問題[J];藥物分析雜志;1996年05期

4 包娜仁;唐冰;王俊科;;磷酸二酯酶Ⅲ抑制劑——奧普力農(nóng)的研究新進(jìn)展[J];中國新藥與臨床雜志;2011年09期

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