Istraživanje kalibracijskih metoda za izravnu desorpciju koja prethodi plinskoj kromatografiji

master's thesis

• Title (english): Investigation of calibration methods for direct desorption prior to gas chromatography
• Author: Ana Modrić
• Mentor: Biljana Nigović (mentor)
• Committee member: Biljana Nigović (predsjednik povjerenstva)
• Committee member: Miranda Sertić (član povjerenstva)
• Committee member: Jasna Jablan (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical analysis); Zagreb
• Defense date and country: 2024-02-23, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

The determination of residual solvents in active substances, excipients, and medicines is mandatory during release testing and advisable throughout the entire drug manufacturing process. Official regulatory bodies recommend headspace-gas chromatography (HS-GC) as the analytical procedure of choice for identification and control of residual solvents in pharmaceuticals. The official headspace-gas chromatography methods assume that the sample can be made into a homogenous solution, which is then analyzed. However, not all compounds can be easily dissolved. A recently presented thermal desorber-gas chromatography (TD-GC) method, developed by the Pharmaceutical Analysis laboratory of KU Leuven and successfully used as an alternative way to determine residual solvents in complex matrices, was adapted and applied to determine residual solvents in different types of modified cellulose beads. Ideally, thermal desorption should be calibrated using gas-phase standards. However, in practice, gas-phase standards are expensive and difficult to obtain, so calibration is routinely done using liquid standards. Calibration becomes critical when thermal desorption is used for direct thermal extraction of residual solvents from solid samples because then the adsorption and desorption pathways of residual solvents in the sample and the reference differ significantly. Inline (ILC) and offline (OLC) liquid calibration were explored as potential calibration methods. After optimization of both methods, offline liquid calibration showed poorer recovery and precision compared to inline liquid calibration. So, inline liquid calibration was chosen as the preferred calibration method for this kind of analysis.

Abstract (croatian)

Određivanje ostatnih otapala u aktivnim farmaceutskim supstancama, ekscipijensima i gotovim lijekovima je obavezno tijekom završnog ispitivanja, a preporučuje se tijekom cijelog procesa proizvodnje lijeka. Regulatorna tijela definiraju headspace–plinsku kromatografiju (HS-GC) kao preferiranu metodu za identifikaciju i određivanje ostatnih otapala u farmaceutskim oblicima. Službena metoda polazi od pretpostavke da se uzorak može otopiti te da se zatim analizira nastala otopina, no ne mogu se sve tvari lako homogenizirati. Nedavno opisana metoda analize plinskom kromatografijom s termalnom desorpcijom (TD-GC), uspješno razvijena u Laboratoriju za farmaceutsku analizu KU Leuvena-a kao alternativna metoda za analizu ostatnih otapala u složenom matriksu, prilagođena je i primjenjena za određivanje ostatnih otapala u više vrsta celuloznih zrnaca. Idealno, termalnu desorpciju bi trebalo kalibrirati standardima u plinskoj fazi, međutim plinski standardi su komplicirani za nabaviti, pa se kalibracija rutinski vrši tekućim standardima. Kalibracija metode je kritični korak u analizi u kojoj se termalni desorber koristi za izravnu desorpciju uzorka u čvrstom stanju, zbog toga što se tada značajno razlikuju adsorpcijski i desorpcijski putevi ostatnih otapala u uzorku i tekućem standardu. Inline (ILC) i offline (OLC) tekućinska kalibracija su istražene kao potencijalne kalibracijske metode. Po završetku optimizacije obiju metoda, offline tekućinska kalibracija je pokazala manji prinos i lošiju preciznost u usporedbi sa inline kalibracijom. Zbog toga je inline tekućinska kalibracija odabrana kao preferirana metoda kalibracije.

• Keywords: calibration; thermal desorption; gas chromatography; residual solvents
• Keywords (english): kalibracija; termalna desorpcija; plinska kromatografija; ostatna otapala
• Language: english
• URN:NBN: urn:nbn:hr:163:734454
• Study programme: Title: Pharmacy - integrated undergraduate and graduate - university study; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: sveučilišni magistar farmacije (sveučilišni magistar farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-06-12 12:23:41