Bazı Antiviral İlaçların Farmasötik Dozaj Şekillerinden ve Plazmadan Sıvı Kromatografisi ile Nicel Analizleri

Abstract

Antiviral drugs are crucial in the treatment of viral infections that pose a threat to human health. During the development and implementation of these drugs, quality control analyses must be carried out with great care. In this thesis, two different methods were developed for the analysis of antiviral drugs from pharmaceutical dosage forms and plasma samples. First, a high-performance liquid chromatography (HPLC) method was developed for the simultaneous determination of six antiviral drugs (emtricitabine, entecavir, favipiravir, ganciclovir, valacyclovir, and valganciclovir). The developed HPLC method was performed using a 50 mM phosphate buffer (pH 4): acetonitrile (90:10, v/v) mobile phase on an Exsil™ Mono 100 C18 column at a flow rate of 0.5 mL/minute. UV detection was performed at 215 nm. The method was validated according to the International Council for Harmonisation (ICH) Q2(R2) guidelines and was found to be linear (R²>0.9938), sensitive, precise (<1.97% RSD), accurate (<1.34% bias), and robust. Furthermore, the method was shown to be successful in terms of its environmental impact (AGREE score: 0.79), practicality (BAGI index: 85), and sustainability (whiteness value: 74.7). Finally, the developed method was applied to commercial preparations and the results obtained were shown to be in agreement with the label content. Secondly, a Solid Phase Microextraction (SPME) coupled with Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) method was developed for the analysis of nine antiviral drugs (acyclovir, emtricitabine, entecavir, ganciclovir, lamivudine, lopinavir, oseltamivir, valacyclovir and valganciclovir) from plasma. The LC-MS/MS method was performed using a C8 column with a gradient elution of water and acetonitrile mobile phases containing 0.1% formic acid. The mobile phase flow rate was set at 0.35 mL/minute and the column oven temperature was set to 40°C. The SPME-LC-MS/MS method was validated according to the ICH 10M guideline. The developed method was found to be linear (R²>0.99) in the range of 5-1000 ng/mL. The LOD values ranged from 2 to 48 ng/mL, while the LOQ values ranged from 10 to 1.45 ng/mL. Intra-day and inter-day precision and accuracy values were found to be less than 15%. In addition, the robustness study showed that the method was stable against small changes. The developed SPME-LC-MS/MS method was successfully applied to patient samples. In conclusion, both methods developed in this thesis provide reliable and effective results in the analysis of antiviral drugs. It is believed that these developed methods will play an important role in the quality control of antiviral drugs and in the monitoring of treatment processes.