Applications of analytical separation techniques in quantitative determinations of pharmaceutical compounds

Doctoral Dissertation uoadl:1668112 335 Read counter

Unit:
Department of Pharmacy
Library of the School of Science
Deposit date:
2017-06-15
Year:
2017
Author:
Kalogria Eleni
Dissertation committee:
Ε. ΠΑΝΤΕΡΗ ΑΝ. ΚΑΘΗΓΗΤΡΙΑ, ΤΜΗΜΑ ΦΑΡΜΑΚΕΥΤΙΚΗΣ, ΕΚΠΑ Επιβλέπουσα
Μέλος τριμελούς συμβουλευτικής επιτροπής
Μ. ΚΟΥΠΠΑΡΗΣ ΚΑΘΗΓΗΤΗΣ, ΤΜΗΜΑ ΧΗΜΕΙΑΣ, ΕΚΠΑ Μέλος τριμελούς συμβουλευτικής επιτροπής
Ε. ΓΚΙΚΑΣ ΕΠΙΚ. ΚΑΘΗΓΗΤΗΣ, ΤΜΗΜΑ ΦΑΡΜΑΚΕΥΤΙΚΗΣ, ΕΚΠΑ Μέλος τριμελούς συμβουλευτικής επιτροπής
A. ΤΣΑΝΤΙΛΗ ΟΜΟΤΙΜΗ ΚΑΘΗΓΗΤΡΙΑ ΤΜΗΜΑΤΟΣ ΦΑΡΜΑΚΕΥΤΙΚΗΣ, ΕΚΠΑ
Ι. ΛΟΥΚΑΣ ΑΝ. ΚΑΘΗΓΗΤΗΣ, ΤΜΗΜΑ ΦΑΡΜΑΚΕΥΤΙΚΗΣ, ΕΚΠΑ
Ν. ΘΩΜΑΪΔΗΣ ΑΝ. ΚΑΘΗΓΗΤΗΣ, ΤΜΗΜΑ ΧΗΜΕΙΑΣ, ΕΚΠΑ

Α. ΒΑΡΒΑΡΕΣΟΥ ΑΝ. ΚΑΘΗΓΗΤΡΙΑ ΤΜΗΜΑ ΑΙΣΘΗΤΙΚΗΣ ΚΑΙ ΚΟΣΜΗΤΟΛΟΓΙΑΣ, ΤΕΙ ΑΘΗΝΑΣ
Original Title:
ΕΦΑΡΜΟΓΕΣ ΔΙΑΧΩΡΙΣΤΙΚΩΝ ΤΕΧΝΙΚΩΝ ΑΝΑΛΥΣΗΣ ΣΕ ΠΡΟΣΔΙΟΡΙΣΜΟΥΣ ΕΝΩΣΕΩΝ ΜΕ ΦΑΡΜΑΚΕΥΤΙΚΗ ΔΡΑΣΗ
Languages:
Greek
Translated title:
Applications of analytical separation techniques in quantitative determinations of pharmaceutical compounds
Summary:
In this work novel analytical separation techniques have been developed and validated for the quantitative determination of pharmaceutical compounds.
Chapter 1, describes the pharmacological characteristics of substances used for anxiety disorders such as benzodiazepines, and in particular the mechanism of action and therapeutic effects of alprazolam. The second subsection of this chapter describes the treatment of hypertension, the mechanism of action and the pharmacokinetic characteristics of aliskiren and hydrochlorothiazide. In the third subsection of the same chapter the mechanism of action of antiperspirant and deodorant products.
Chapter 2, describes the operating principles of liquid chromatography - mass spectrometry which is a frequently used hyphenated analytical technique in the field of pharmaceutical analysis. A thorough description of the instrumentation including atmospheric pressure ionization sources, mass analyzers and mass detectors is also included in this chapter.
In chapter 3, an overview of the HILIC separation system comparing it to other chromatographic modes is described. Furthermore, the progress in understanding the separation mechanism along the new trends in HILIC packing materials is discussed. Characteristic applications of HILIC mode chromatography in the field of pharmaceutical analysis are also presented.
Chapter 4, refers to the general principles for the development of an stability-indicated HPLC method. The second part of this chapter is dedicated to a basic introduction to the chemical kinetics of simple reaction systems in solution.
In Chapter 5, a hydrophilic interaction liquid chromatography /positive ion electrospray-mass spectrometry (HILIC-ESI/MS) method has been developed and fully validated for the quantification of alprazolam and its main metabolite, a-hydroxy-alprazolam, in human plasma. The assay is based on 50 μL plasma samples, following liquid-liquid extraction. All analytes and the internal standard (tiamulin) were separated by hydrophilic interaction liquid chromatography using an X-Bridge-HILIC analytical column (150 x 2.1 mm i.d., particle size 3.5μm) under isoscratic elution. The mobile phase was composed of a 7% 10 mM ammonium formate water solution in acetonitrile and pumped at a flow rate of 0.20 mL min-1. Running in positive electrospray ionization and selected ion monitoring (SIM) the mass spectrometer was set to analyze the protonated molecules [M+H]+ at m/z 309, 325 and 494 for alprazolam, a-hydroxy-alprazolam and tiamulin (internal standard) respectively. The assay was linear over the concentration range of 2.5-250 ng mL-1 for alprazolam and 2.5-50 ng mL-1 for a-hydroxy alprazolam. The method is the first reported application of HILIC in the analysis benzodiazepines in human plasma. With a small sample size (50 μL human plasma) and a run time less than 10 min for each sample the method can be used to support a wide range of clinical studies concerning alprazolam quantification.
In Chapter 6, chemical kinetics of aliskiren and hydrochlorothiazide have been investigated under acidic, basic and oxidative comditions. The rate constants (k) along with half-life’s, t½, obtained from the acidic, basic and oxidative stressed samples of aliskiren and hydrochlorothiazide have been determined. For this purpose a reversed-phase HPLC method on a silica-based phenyl analytical column have been partially validated and quantification of the analytes was based on peak area values. It was found that both compounds follow pseudo-first order reaction kinetics. The degradation of aliskiren under basic conditions proceeded slowly with one unknown degradation peak at 2.99 min. In the acid stressed samples, two unknown degradation peaks appeared at retention times 2.22 min and 14.45 min. Under oxidative conditions, two unknown degradation products appeared at 3.13 and 7.89 min along with a strong interaction peak at 0.82 min that is due to the presence sodium peroxide in the sample. Degradation of hydrochlorothiazide did not reveal any degradation product that could be detected at the wavelength used for this assay.
Chapter 7 describes the development and validation of a selective high-performance liquid chromatography method that allows, after liquid-liquid extraction and pre-column derivatization reaction with quercetin, the quantification of aluminium chlorohydrate in antiperspirant creams. Chromatographic separation was achieved on an XTerra MS C18 analytical column (150mm x 3,0 mm i.d., particle size 5 μm) using a mobile phase of acetonitrile: water (15:85, v/v) containing 0.08% trifluoroacetic acid at a flow rate of 0.30 mL min-1. Ultraviolet (UV) spectrophotometric detection at 415nm was used. The assay was linear over a concentration range of 3.7-30.6 μg mL-1 for aluminium. The method was used to quantify aluminium in antiperspirant creams containing 11 %, 13 % and 16 % (w/w) aluminium chlorohydrate, respectively.
Main subject category:
Science
Other subject categories:
Pharmacy
Keywords:
LC-MS, HILIC, benzodiazepines, aluminium, chemical kinetics
Index:
No
Number of index pages:
0
Contains images:
No
Number of references:
235
Number of pages:
306
ΕΛΕΝΗΚΑΛΟΓΡΗΑ_IP15.06.17.pdf (5 MB) Open in new window