Hidroklorotiazid içeren farmasötik preparatlardaki etken maddelerin kemometrik yöntemlerle miktar tayinleri
Quantitative determination of active compounds in pharmaceutical preparations containing hydrochlorothiazide by using chemometric methods
Yazar: ÖZGÜR ÜSTÜNDAĞ
Danışman: Y.DOÇ.DR. ERDAL DİNÇ
Ankara Üniversitesi / Sağlık Bilimleri Enstitüsü / Analitik Kimya Ana Bilim Dalı
Derece: Yüksek Lisans, 2003
Konu: Eczacılık ve Farmakoloji = Pharmacy and Pharmacology

Özet:
262 ÖZET Hidroklorotiyazid İçeren Farmasötik Preparatlardaki Etken Maddelerin Kemometrik Yöntemlerle Miktar Tayinleri Bu çalışmada altı kemometrik yöntem (bivariate calibration (BC), multilinear regression calibration (MLRC), classical least-squares (CLS), inverse least-squares (ILS), principal component regression (PCR) and partial least-squares (PLS) yöntemleri hidroklorotiazid- spironolakton, hidroklorotiazid-amilorid hidroklorür ve hidroklorotiazid-kaptopril karışımlarını içeren farmasötik preparatlara başarıyla uygulandı. 1. Hidroklorotiazid-Spironolakton Karışımının Analizi Farmasötik tablet preparatında bulunan hidroklorotiazid ve spironolaktonun aynı anda miktar tayinleri BC, MLRC, CLS, ILS, PCR ve PLS yöntemleri ile gerçekleştirildi. Hidroklorotiazid ve spironolakton için 6-20 p.g/mL doğrusal çalışma aralığında bivariate kalibrasyon için 240 ve 270 nm optimum dalga boyları olarak seçildi. Kurulan kalibrasyon hidroklorotiazid ve spironolakton içeren farmasötik tablet preparatına uygulandı. MLRC yönteminde hidroklorotiazid ve spironolaktonun karışımı seçilen 10 dalga boyunda (225 nmden 295 nmye kadar) elde edilen lineer regresyon fonksiyonlarının kalibrasyonu kullanılarak analiz edildi. Kalibrasyon seti için 25 noktalı karışım dizaynına karşılık gelen 2-20 jig/mL hidroklorotiazid ve spironolaktonu içeren kalibrasyon sistemi kullanılarak CLS, ILS, PCR ve PLS kalibrasyonları 0. dereceden absorbsiyon spektrumları için 220-290 nm dalga boyu aralığında 15 noktadaki absorbans ölçümleri ile elde edildi.263 2. Hidroklorotiazid-Amilorid Hidroklorür Karışımının Analizi BC, MLRC, CLS, ILS, PCR ve PLS metodları farmasötik tablet preparatındaki hidroklorotiazid ve amilorid hidroklorürûn aynı anda miktar tayinlerinde kullanıldı. Bivariate kalibrasyonu için absorbans değerleri hidroklorotiazid ve amilorid hidroklorürün herbir karışımı için Kaiser tekniği ile bulunan optimum iki dalga setinde (270 ve 290 nm) ölçüldü. BC yöntemi ile hidroklorotiazid ve amilorid hidroklorür farmasötik tablet preparatında tayin edildi. Karışımdaki herbir ilaç için 10 lineer regresyon fonksiyonu 10 dalga boyu setinde (235 nm'den 280 nmye kadar) absorbansların ölçümü ile elde edildi. Tabletlerdeki hidroklorotiazid ve amilorid hidroklorürün aynı anda miktar tayinleri multilineer regresyon kalibrasyon yöntemi kullanılarak başarıldı. CLS, ILS, PCR ve PLS algoritmalarına göre kalibrasyonlar 25 noktalı karışım dizaynına karşılık gelen 4-28 jxg/mL hidroklorotiazid ve 2-10 ng/mL amilorid hidroklorür içeren kalibrasyon seti için 220 nm'den 385 nmye kadar dalga boyu aralığında 34 noktada absorbansların ölçümü ile kuruldu. Bu kemometrik kalibrasyonlar hidroklorotiazid ve amilorid hidroklorürü içeren bir farmasötik preparatın kantitatif analizine başarıyla uygulandı.

Abstract:
265 SUMMARY Quantitative Determination of Active Compounds in Pharmaceutical Preparations Containing Hydrochlorothiazide by Using Chemometric Methods. In this study, six chemometrics methods, bivariate calibration (BC), multilinear regression calibration (MLRC), classical least-squares (CLS), inverse least-squares (ILS), principal component regression (PCR) and partial least-squares (PLS) were satisfactorily applied to the quantitative analysis of binary mixtures of hydrochlorothiazide- spironolactone, hydrochlorothiazide-amiloride hydrochloride and hydrochlorothiazide-captopril in pharmaceutical preparations. 1. Analysis of Hydrochlorothiazide-Spironolactone Mixture Simultaneous determination of hydrochlorothiazide and spironolactone in a pharmaceutical tablet preparation was carried out by BC, MLRC, CLS, ILS, PCR and PLS methods. Bivariate calibration, an optimum two-wavelength set was selected as 240 and 270 nm for the bivariate calibration in the working range 6-20 ng/mL for both drugs. The constructed calibration was applied to pharmaceutical tablet preparation containing hydrochlorothiazide and spironolactone. In the MLRC method, the mixture of hydrochlorothiazide and spironolactone was simultaneously analysed by using the calibration of multilinear regression functions at ten-wavelength set (from 225 nm to 295 nm). By using a calibration set containing 2-20 p.g/mL hydrochlorothiazide and spironolactone corresponding to 25 point mixture design, CLS, ILS, PCR and PLS calibrations were constructed by measuring the absorbance values at 15 points in the wavelength266 range 220-290 nm for the zero-order spectra. The quantitative analysis of hydrochlorothiazide and spironolactone was accomplished by these calibrations. 2. Analysis of Hydrochlorothiazide-Amiloride hydrochloride Mixture BC, MLRC, CLS, ILS, PCR and PLS methods were subjected to the simultaneous determination of hydrochlorothiazide and amiloride hydrochloride in a pharmaceutical tablet preparation. In case of the bivariate calibration, absorbance values were measured at the optimum two-wavelength set found by Kaiser's technique for each mixture of hydrochlorothiazide and amiloride (270 and 290 nm). Hydrochlorothiazide and amiloride were determined in a pharmaceutical tablet preparation. In the MLRC method, ten linear regression functions for each drug were obtained by measuring the zero-order absorbances at ten- wavelengths set (from 235 nm to 280 nm). Statistical data of ten linear regression functions were used for the calibration of multilinear regression functions. Simultaneous analysis of hydrochlorothiazide and amiloride hydrochloride in tablets was achieved by using the calibration of multilinear regression functions. According to the algorithms of CLS, ILS, PCR and PLS, the calibrations were constructed by measuring the zero-order absorbances at 34 points in the range of the wavelength from 220 nm to 385 nm for calibration set containing 4-28 p.g/mL hydrochlorothiazide and 2-10 pg/mL amiloride hydrochloride corresponding to 25 point mixture design, These chemometric calibrations were applied to the quantitative analysis of a267 pharmaceutical preparation containing hydrochlorothiazide and amiloride hydrochloride. 3. Analysis of Hydrochlorothiazide-Captopril Mixture Simultaneous quantitative analysis of hydrochlorothiazide and captopril in a pharmaceutical tablet preparation was made by BC, MLRC, CLS, ILS, PCR and PLS methods. Bivariate calibration was constructed by measuring the absorbance values at two-wavelength set (220 and 272 nm) in the working range 3-15 jxg/mL for hydrochlorothiazide and 4-20 p,g/mL for captopril. This calibration was applied to the simultaneous analysis of hydrochlorothiazide and captopril in a pharmaceutical tablet preparation. Calibration of multilinear regression functions was calculated by using the measurements at fifteen-wavelength set (from 210 nm to 300 nm). The constructed calibration was applied to a pharmaceutical preparation containing hydrochlorothiazide-captopril. Calibration set containing 0-15 p.g/mL hydrochlorothiazide and 0-20 jAg/mL captopril were randomly prepared by using the stock solutions of hydrochlorothiazide and captopril for chemometric calibrations. CLS, ILS, PCR and PLS calibrations were constructed by measuring the absorbance values at 13 points in the wavelength range 215-300 nm for the zero-order spectra. The quantitative determination of hydrochlorothiazide and captopril in a pharmaceutical preparation was realized by these calibrations.268 Key words : Chemometric methods, quantitative determination, hydrochlorothiazide, spironolactone, amiloride hydrochloride, captopril, pharmaceutical preparation.