New Spectrophotometric Analytical Methods for Determination Some Cardiovascular Drugs in Pharmaceutical Formulations

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علوم بحتة وطبيعية

الملخص

The efforts in this thesis have represented a big challenge to develop new and cost effective analytical spectrophotometric methods for the determination of five medicationscomponents belonging to numerous categories specializing in treating cardiovascular diseases(CVDs) involves; Atorvastatin Calcium (ATOR), Rosuvastatin Calcium (RUSV),Amlodipine Besylate (AMLO), Atenolol (ATEN), and Hydrochlorothiazide (HCTZ).Thestudy, which included the estimation of the studied drugs individually and simultaneously intheir pure forms, pharmaceutical formulations (tablets) serum and urine.In the individual estimation method developing a novel indirect reversespectrophotometric method for determining mentioned drugs in their pure forms andpharmaceutical formulations was described. It was based on the oxidation of the drug with afixed excess concentration of KIO4 in acidic HCl solution, consequently the residualunreacted oxidizing agent (KIO4) reacts with the p-ansidine reagent, as a result yellowish orange soluble color complex was formed with 538 nm λmax and measuredspectrophotometrically. The indicated λmax absorption peak has been adopted as a baseline toconstruct the reverse estimate at 425nm as a new inverse peak for the determination of thedrugs under study. The absorption intensity of the inverse peak was inversely related to thedrugs concentrations. Three methods were used to find optimum conditions for theexperiment; univariate and multivariate methods (Central Composite Design (CCD) and Box Benhken Design (BBD)). The influence of three factors has been studied and optimized fortheir effective impact on the course of the selected methods and these factors are: oxidantvolume (mL), p-anisidine concentration (w/v) and acid volume (mL). The optimal conditionsthese parameters are 1.5 mL of (3 % w/v) KIO4, (0.08 % w/v) of p-anisidine and 0.6 mL of(1N) HCl for univariate method, 1.5 mL of (3 % w/v) KIO4, (0.07 % w/v) of p-anisidine and0.7 mL of (1N) HCl by (CCD) method, and 1.525 mL of (3 % w/v) KIO4, (0.075 % w/v) ofp-anisidine and 0.55 mL of (1N) HCl by (BBD) method. Calibration curves were constructedfor all drugs by plotting absorbances signals against concentration (µg.mL-1) at 425 nmand found to be linear over the concentration range (5-170 µg.mL-1), (25-170 µg.mL-1), (8-148 µg.mL-1), (12-150 µg.mL-1) and (3-210 µg.mL-1) for ATOR, RUSV, AMLO, ATEN,and HCTZ, respectively via univariate method, (5-185 µg.mL-1), (15-195 µg.mL-1), (5-158µg.mL-1), (3-160 µg.mL-1) and (1-230 µg.mL-1) for ATOR, RUSV, AMLO, ATEN, andHCTZ, respectively via CCD method and (3-188 µg.mL-1), (8-208 µg.mL-1), (5-158 µg.mL-VII1), (3-160 µg.mL-1) and (1-240 µg.mL-1) for ATOR, RUSV, AMLO, ATEN, and HCTZ,respectively via BBD method.The limit of detection (LOD) and limit of quantification (LOQ) for the mentioned drugsby those methods were found be in the range (0.14384 – 0.19306 µg.mL-1) LOD and (0.43590- 0.58503 µg.mL-1) LOQ via univariate method, (0.11423 – 0.17973 µg.mL-1) LOD and(0.34615 - 0.54466 µg.mL-1) LOQ via CCD method, and (0.0991– 0.18615 µg.mL-1) LODand (0.3003 – 0.56410 µg.mL-1) LOQ via BBD method. Validity of all methods were checkedby measuring relative standard deviation (RSD %) relative error (RE %) and it was foundRSD% < 5% while RE% < 4%,. The analysis results do not show any interference from theexcipients by using these techniques. Therefore ATOR, RUSV, AMLO, ATEN and HCTZwere suitable for estimation in their pharmaceutical formulation.Under the title “simultaneous determination of ATOR, RUSV, AMLO, ATEN and HCTZdrugs” estimation of the five drugs in their binary, tertiary, quaternary and pentanary mixturesby six develop methods (first (D1) and second (D2) derivative spectrophotometric, derivativeratio spectrophotometry method (DRS), artificial neural network (ANN), partial least squares(PLS), and principal component regression (PCR) techniques) were described.Derivative spectrophotometric techniques (D1 and D2) were developed for thesimultaneous determination of ATOR, RUSV, AMLO, ATEN and HCTZ drugs in their binarymixtures. It was found that all cited drugs could be determined by both modes of derivative.The zero crossing technique was employed in D1 measurements, using peak height to baselineat 294.6, 234, 253.6, 284.2 and 261.4 nm for ATOR, RUSV, AMLO, ATEN and HCTZrespectively, same procedure was applied in D2 by using the peak height to baseline at 311.6,342.8, 257.7, 287.8 and 234 nm for ATOR, RUSV, AMLO, ATEN and HCTZ respectively.Derivative ratio spectrophotometry method (DRS) was applied for the simultaneousestimation of ATOR, RUSV, AMLO, ATEN and HCTZ in their tertiary, quaternary andpentanary mixtures. A 308 synthetic mixtures were prepared and distributed as 88, 140 and80 from tertiary, quaternary and pentanary mixtures respectively, using Design ExpertsSoftware (DES) version (2019) according to Mixture Design (MD). The first derivative ratioof amplitude spectrum was applied for constructing the calibration graph for drugs in theirpentanary mixtures. The calibration graphs of D1-amplitude spectrum were constructed in therange of (5 – 30 μg.mL-1) at 283.2 nm for ATOR, (5 – 35 μg.mL-1) at 318.2 nm for RUSV, (3– 28 μg.mL-1) at 404.2 nm for AMLO, (5 – 30 μg.mL-1) at 233.2 nm for ATEN and (5 – 40μg.mL-1) at 263.6nm for HCTZ. Quaternary mixtures were composed as a divisor, where halfVIIIof the linear concentrations of each drug were used in that composition. The result of relativestandard deviation percentage (RSD %) and relative error percentage (RE %) were in theranges (0.151% - 3.725%) and (-3.94% - 4.98%) for tertiary mixtures, (0.399% - 3.87%) and(-5.423% - 4.62%) for quaternary mixtures and (0.327% - 4.034%) and (-6.178% - 6.956%)for pentanary mixtures respectively.ANN, PLS and PCR techniques were used as chemometric technique for simultaneousspectrophotometric estimation of ATOR, RUSV, AMLO, ATEN and HCTZ in their tertiary,quaternary and pentanary mixtures. The first section in the methodology of the techniquesincludes the construction of a calibration (training) set of spectrophotometric data, obtainedfrom zero orders calibration graph, composing of 60 mixtures chosen randomly by the designexperts software (DES). The absorbance data matrices related to the weighted ofconcentration data matrices for each of the 60 mixtures were obtained by the measurementsof absorbance in the range 200-400 nm with a scan speed of 10 nm.sec-1, averaging of 0.2nm, bandwidth of 1.8 nm, and data interval of 0.1 nm against solvent blank. The ANN, PLSand PCR regression models were built with the Assistance of Origin Pro software version(2015) program and the concentration of the five drugs were then predicted. The result ofrelative standard deviation percentage (RSD %) and relative error percentage (RE %) were inthe ranges (0.019% - 1.219%) and (-0.542% - 0.644%) for ANN, (0.048% - 3.1%) and (-3.158% 1.345%) for PLS and (0.087% - 2.642%) and (-4.612% - 4.817%) for PCRrespectively. The proposed method was successfully applied in the simultaneousdetermination of ATOR, RUSV, AMLO, ATEN and HCTZ in their sample of laboratorysynthetic mixtures, spike in serum, and urine.

روابط وملفات

التعريف والنوع

رقم الوثيقة

fd3ceef7-cd2a-4b3a-b44a-df1361acbaa3

رقم العقد

0

نوع الوسائط

Crawler

نوع المحتوى

الرسائل العلمية

صيغة المصدر

رسائل دكتوراة

نوع الملف

pdf text

أسماء الملفات

2306233_1.pdf

بيانات النشر

ترجمة العنوان

طرائق تحليلية طيفية جديدة لتقدير بعض ادوية الاوعية الدموية القلبية باشكالها الصيدلانية

ألقاب المؤلفين

[{"name_ar":"Al-Mashhadany Marwan Abdul-Aziz Hassan","title_ar":"اعداد","title_en":"Preparation"},{"name_ar":"Khalid FarouqAbdul-Khafuor","title_ar":"اشراف","title_en":"Supervision"},{"name_ar":"Rebwar Omer Hassan","title_ar":"اشراف","title_en":"Supervision"}]

اللغة

English

المصدر والدورية

اسم المصدر

New Spectrophotometric Analytical Methods for Determination Some Cardiovascular Drugs in Pharmaceutical Formulations

المحتوى والصفحات

عدد الصفحات

0

كلمات الباحثين

Analytical Methods

إشراف وإعداد

الإشراف

Khalid FarouqAbdul-Khafuor, Rebwar Omer Hassan

الإعداد

Al-Mashhadany Marwan Abdul-Aziz Hassan

الاقتباسات الببليوغرافية