Određivanje razgradnih produkata diazepama spektrometrijom masa visoke razlučivosti

master's thesis

• Title (english): Determination of diazepam degradation products by high resolution mass spectrometry
• Author: Iva Karačić
• Mentor: Dragana Mutavdžić Pavlović (mentor)
• Committee member: Dragana Mutavdžić Pavlović (predsjednik povjerenstva)
• Committee member: Tatjana Gazivoda Kraljević (član povjerenstva)
• Committee member: Marija Vuković Domanovac (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2018-09-27, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry; Analytic Chemistry

Abstract

Svaki lijek ili farmaceutik sadrži razna organska ili anorganska onečišćenja te razgradne produkte koji u lijeku obično zaostaju iz proizvodnog postupka, nastaju tijekom izrade ljekovitog oblika ili skladištenjem lijeka. Razgradni produkti mogu nastati djelovanjem svjetla, temperature, u prisutnosti vode ili promjenom pH, a mogu nastati i tijekom izrade ili čuvanja farmaceutskog dozirnog oblika. Njihova prisutnost, čak i u vrlo malim količinama, može utjecati na stabilnost, djelotvornost i sigurnost primjene lijeka. U ovom radu razvijena je brza i učinkovita metoda za analizu onečišćenja i razgradnih produkata farmaceutika diazepama u farmaceutskoj otopini. Za određivanje i kvantifikaciju diazepama i njegovih razgradnih produkata koristi se tekućinska kromatrografija ultravisoke djelotvornosti (UHPLC) spregnuta sa spektrometrijom masa (LC-MS/MS). Pomoću razvijene metode određeni su razgradni produkti nastali forsiranom razgradnjom diazepama u kiselini, lužini, vodikovom peroksidu i netretiranom uzorku, ispitan je utjecaj temperature i svjetlosti na razgradnju te su pretpostavljene strukture i način fragmentacije dobivenih razgradnih produkata. Za određivanje optimalnih uvjeta kromatografskog odjeljivanja metodom UHPLC (temperatura kolone, sastav pokretne faze, vremenski gradijent, pH) korišten je računalni program Drylab.

Abstract (english)

Each drug or pharmaceutical contains various organic or inorganic contaminants and degradable products that typically lag behind in drug during the manufacturing process, preparation of a medicated form or by storage of the drug. The degradable products can be generated under the influence of light, temperature, water or pH change, and may also occur during the preparation or storage of the pharmaceutical dosage form. Even in very small quantities, the presence of contamination can affect the efficacy and safety of drug use. In this study, a quick and efficient method for analysis of contaminants and degradation products of diazepam was developed. High efficiency liquid chromatography (UHPLC) coupled with mass spectrometry (LC-MS/MS) was used for determination and quantification of diazepam and his degradation products. Degradation products generated by forced degradation of diazepam in acid, alkaline solution, hydrogen peroxide, untreated sample, and under the influence of temperature and light, were determinated by the developed UHPLC method. Also, based on the developed method, their structures and possible pathways of fragmentation were assumed. Drylab software was used to determine the optimal conditions of chromatographic separation method (column temperature, composition of mobile phase, time gradient, pH).

• Keywords: diazepam; onečišćenja; razgradni produkti; UHPLC metoda; MS/MS
• Keywords (english): diazepam; contaminants; degradation products; UHPLC method; MS/MS
• Language: croatian
• URN:NBN: urn:nbn:hr:149:817288
• Study programme: Title: Applied Chemistry - Graduate study; specializations in: Environmental chemistry and green technologies, Advanced materials and technologies, Applied organic chemistry; Course: Applied organic chemistry; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra primijenjene kemije (magistar/magistra primijenjene kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2020-10-29 11:39:53