Anjiyotensin II reseptör antagonistleri içeren farmasötik preparatlardaki etkin maddelerin spektral olarak ?Sürekli dalgacık dönüşüm? yöntemleriyle miktar tayinleri
Özet
The main aim of this Ph.D. thesis is to develop new signal processing methods for the quantitative determination of active compounds in the commercial pharmaceutical preparations containing angiotensin II receptor antagonists without using any priory separation step. In this context, new signal processing methods based on the combined use of the Continuous Wavelet Transform (CWT) with the ratio spectra and zero crossing technique were developed for the simultaneous quantitative analysis of the commercial pharmaceutical preparations containing Irbesartan-Hydrochlorothiazide, Candesartan-Hydrochlorothiazide and Losartan-Hydrochlorothiazide combinations (IRB-HCT, CAN-HCT and LOS-HCT, respectively).Priory to analysis of IRB and HCT in samples, various CWT familes at different orders and scale parameters (a) were tested and DB5-CWT (a=128) and SYM5-CWT (a=200) combined with zero crossing and HAAR (a=32) and BIOR1.3 (a=50) with ratio spectra treatment were found to be suitable signal processing method giving the best recovery results for the determinations.For the simultameous analysis of IRB and HCT in samples, the calibration graphs by using SYM-CWT and DB5-CWT with zero crossing (ZC) was obtained by measuring the CWT amplitudes at 243.0 nm and 243.3 nm for IRB and 273.8 and 277.7 nm for HCT, respectively.In the application of HAAR-CWT and BIOR1.3-CWT to the ratio spectra of IRB/HCT and HCT/IRB, the calibration equations were calculated by using the relationship between the concentration and CWT-amplitudes at 236.7 and 235.9 for IRB and 266.0 and 262.8 nm for HCT, respectively. These CWT methods based on the ratio spectra were named as RS-HAAR-CWT and RS-BIOR1.3-CWT.The validation of the proposed signal processing methods, namely SYM-CWT-ZC, DB5-CWT-ZC, RS-HAAR-CWT and RS-BIOR1.3-CWT for the analysis of IRB and HCT compounds were performed by analysing various synthtetic mixtures, by using interday-intraday tests and standard addition technique.In addition, the ratio spectra first derivative spectrophotometry (RS-DS1) was applied to the same samples containing IRB and HCT. As a comparison method, ultra performance liquid chromatography (UPLC) was developed for the determination of IRB and HCT in their mixtures. UPLC method was validated by using he validation parameters as well as CWT signal processing methods.The developed SYM-CWT-ZC, DB5-CWT-ZC, RS-HAAR-CWT, RS-BIOR1.3-CWT, RS-DS1 and UPLC metods were applied to the quantitative analysis of IRB and HCT in tablets.In the analysis of CAN-HCT mixture, SYM2-CWT (a=128) and RBIOR2.2-CWT (a=90) based on zero crossing technique and HAAR-CWT (a=64) and MEXH (a=64) based on the ratio spectra were found to be appropriate for the simultaneous analysis of samples containing CAN and HCT after testing several wavelet familes to get up the best recovery results.In the application of SYM2-CWT-ZC and RBIOR2.2-CWT-ZC, the calibration graphs were calculated by using SYM2-CWT and RBIOR2.2-CWT amlitudes at 242.8 and 238.9 nm for CAN and 274.7 and 271.4 nm for HCT, respectively. In cases of RS-HAAR-CWT and RS-MEXH-CWT methods, calibration equations were obtained by usinh the ratio spectra-HAAR-CWT and the ratio-MEXH-CWT signals at at 244.5 and 255.6 nm for CAN and 280.0 and 250.0 nm for HCT, respectively.The validity of the proposed signal processing methods, SYM2-CWT-ZC and RBIOR2.2-CWT-ZC, RS-HAAR-CWT and RS-MEXH-CWT were carried out by using the synthtetic mixtures and interday-intraday analysis and standard addition techniques.First derivative spectrophotometry (DS1) and ratio spectra first derivative spectrophotometry (RS-DS1) as traditional spectrophotometric methods were used for the simultaneous analysis of the mixtures consisting of CAN and HCT drugs.For a comparison, a new UPLC method for the analysis of CAN-HCT mixtures was developed and validated by using the above mentioned analytical validation and statistical parameters.In case of LOS and HCT in samples, DEMY-CWT-ZC (a=120), SYM5-CWT (a=148), RS-COIF1-CWT (a=100), RS-MEXH-CWT (a=64), RS-HAAR-CWT (a=96), RS-SYM5-CWT (a=100) approaches were developed for the spectral quantitative analysis of the binary mixtures of LOS and HCT compounds. After the method validation procedure, the proposed methods were applied to the analysis of LOS-HCT tablets. In addition, the ratio spectra first derivative spectrophotometry was used for the quntitative analysis of LOS and HCT in samples. The CWT methods developed in this study are very easy to apply, sensitive, very useful and yet very cheap.The experimental results obtained by appliying the developed CWT signal procesing and traditional derivative methods to the analysis of tablets were statistically compared with those obtained by the devoloped UPLC methods and the literature HPLC method. As a result, a good agrement was observed for the tablet determination results.This study indicates that all the proposed methods in this study can be used for t