本文選題：喹諾酮類藥物 + LC-MS　； 參考：《重慶大學(xué)》2014年碩士論文

【摘要】：喹諾酮類藥物是目前臨床上廣泛使用的一種藥物，主要用于治療由各種細(xì)菌引起的感染性疾病，為保證臨床用藥的安全性和有效性，此類藥物的質(zhì)量控制顯得尤為重要。但在藥品的研究、生產(chǎn)、供應(yīng)和使用過(guò)程中，由于受到各種外界環(huán)境的影響，藥品本身可能會(huì)發(fā)生降解或變質(zhì)，為了保證藥品的安全、有效和質(zhì)量可控，，需要一種可快速、簡(jiǎn)便、靈敏、準(zhǔn)確分析藥品質(zhì)量的方法。隨著高分辨質(zhì)譜的發(fā)展，液相色譜質(zhì)譜聯(lián)用技術(shù)在藥物結(jié)構(gòu)、穩(wěn)定性的研究中顯示出了獨(dú)特的優(yōu)勢(shì)，可提供精確的分子量以及特征碎片峰推測(cè)鑒定出目標(biāo)化合物的結(jié)構(gòu)，已成為復(fù)雜基質(zhì)中未知物結(jié)構(gòu)鑒定和藥品質(zhì)量控制的一個(gè)重要的方法。 本課題首先對(duì)鹽酸左氧氟沙星、鹽酸環(huán)丙沙星、鹽酸恩諾沙星、鹽酸沙拉沙星、諾氟沙星等五種常用喹諾酮類藥物的二級(jí)質(zhì)譜裂解行為進(jìn)行研究，發(fā)現(xiàn)這類喹諾酮類藥物的斷裂方式主要為一些中性小分子，如H2O、CO2、HF、CO、CH2CH2和環(huán)丙烯等的丟失，以及哌嗪基部分的四元環(huán)氫重排。然后，采用液相色譜質(zhì)譜聯(lián)用法（LC-MS）對(duì)在強(qiáng)酸、強(qiáng)堿、氧化、高溫、高濕和光照等藥典規(guī)定的強(qiáng)制條件下，分別對(duì)放置10天的六種喹諾酮類原料藥進(jìn)行質(zhì)量跟蹤分析，且通過(guò)多級(jí)質(zhì)譜分析對(duì)其降解產(chǎn)物進(jìn)行鑒定，實(shí)驗(yàn)結(jié)果表明：高溫、光照和氧化對(duì)這六種喹諾酮類藥物的影響較為顯著。高溫條件下，恩諾沙星、諾氟沙星、鹽酸環(huán)丙沙星和鹽酸沙拉沙星產(chǎn)生的降解產(chǎn)物較多，多為哌嗪基部分開(kāi)環(huán)，在雙鍵上引入CO的產(chǎn)物，鹽酸恩諾沙星和鹽酸左氧氟沙星未見(jiàn)明顯的降解現(xiàn)象；光照條件下，鹽酸左氧氟沙星產(chǎn)生五種明顯的降解產(chǎn)物，多為哌嗪基部分重排和中性分子丟失的產(chǎn)物；氧化條件對(duì)除鹽酸環(huán)丙沙星外的其余五種原料藥均有影響，其中對(duì)恩諾沙星的氧化作用大于鹽酸恩諾沙星；強(qiáng)堿條件下除鹽酸左氧氟沙星產(chǎn)生m/z336，鹽酸沙拉沙星產(chǎn)生m/z751的降解峰外其他四種原料藥均未發(fā)生明顯的降解現(xiàn)象；高濕和強(qiáng)酸條件對(duì)這六種原料的影響不顯著。 通過(guò)考察高濕、高溫、光照、氧化、強(qiáng)酸和強(qiáng)堿這六種影響因素對(duì)喹諾酮類原料藥的影響，可以比較全面地了解其穩(wěn)定特性，從而為該類藥物的制劑處方、工藝的設(shè)計(jì)，以及產(chǎn)品儲(chǔ)存等條件的確定提供科學(xué)的理論依據(jù)。
[Abstract]:Quinolones are widely used in clinic at present. They are mainly used to treat infectious diseases caused by bacteria. In order to ensure the safety and effectiveness of clinical drugs, the quality control of these drugs is particularly important. However, in the course of research, production, supply and use of drugs, due to the influence of various external environments, the drugs themselves may degrade or deteriorate. In order to ensure the safety, effectiveness and quality control of the drugs, a kind of rapid and efficient medicine is needed. A simple, sensitive and accurate method for the analysis of drug quality. With the development of high resolution mass spectrometry, liquid chromatography-mass spectrometry (LC-MS) has shown unique advantages in the study of drug structure and stability, which can provide accurate molecular weight and characteristic fragment peaks to identify the structure of the target compounds. It has become an important method to identify the structure of unknown substances in complex matrix and to control drug quality. The second order mass spectrometric cracking behavior of levofloxacin hydrochloride, ciprofloxacin hydrochloride, enrofloxacin hydrochloride, salafloxacin hydrochloride and norfloxacin were studied. It is found that the cleavage patterns of these quinolones are mainly due to the loss of some neutral small molecules such as H _ 2O _ 2 CO _ 2H _ (2) H _ (2) H _ (2) Ch _ (2) Ch _ (2) Ch _ (2) and cyclopropene, and the quaternary cyclic hydrogen rearrangement of piperazine group. Then, the quality of six quinolones raw materials placed for 10 days under the compulsory conditions of strong acid, strong base, oxidation, high temperature, high humidity and light were analyzed by liquid chromatography-mass spectrometry (LC-MS). The degradation products were identified by multistage mass spectrometry. The results showed that the effects of high temperature, light and oxidation on the six quinolones were significant. Under high temperature, enrofloxacin, norfloxacin, ciprofloxacin hydrochloride and salafloxacin hydrochloride produced more degradation products, most of them were piperazine group partial ring opening, and CO was introduced into the double bond. The degradation of enrofloxacin hydrochloride and levofloxacin hydrochloride was not obvious, and under illumination, levofloxacin hydrochloride produced five obvious degradation products, most of which were the products of piperazine partial rearrangement and neutral molecule loss. Besides ciprofloxacin hydrochloride, the oxidation of enrofloxacin was more effective than that of enrofloxacin hydrochloride. Except levofloxacin hydrochloride produced m / z 336 and salafloxacin hydrochloride produced m/z751 degradation peak, no obvious degradation occurred in the other four raw materials except levofloxacin hydrochloride under strong alkali condition, but the effect of high humidity and strong acid on these six raw materials was not significant. By examining the effects of high humidity, high temperature, light, oxidation, strong acid and strong base on quinolones, we can fully understand the stability of quinolones, so as to design the formulation and process of this kind of drugs. And product storage and other conditions to provide a scientific theoretical basis.
【學(xué)位授予單位】：重慶大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：O657.63;R917

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