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Determination of Transkarbam 12 and Its Impurities Using HPLC Coupled with MS Detection
Folbrová, Jana ; Sochor, Jaroslav (advisor) ; Kučera, Radim (referee)
Determination of Transkarbam 12 and Its Impurities Using HPLC Coupled with MS Detection Master paper Mgr. Jana Folbrová Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Chemistry and Drug Control, Heyrovského 1203, Hradec Králové This paper deals with determination of Transakrbam 12 (T 12), its three impurities ε-aminocaproic acid (Ak), ε-caprolactam (Ka) and the adduct of T 12 and Ak, and of the internal standard which was 8-aminooctanoic acid (Ao). Transkarbam 12 is a new substance which belongs to the group of accelerators of transdermal penetration. Such substances facilitate or enable the drugs passing through the skin barrier into the system circulation. Chromatographic conditions were optimised for determination of the above listed substances using HPLC coupled with MS detection. Using the direct injection MS and MS/MS spectra of all substances were taken and conditions of their detection were optimised. Chromatographic separation was achieved using Luna Phenyl-Hexyl analytical column (5 μm, 150 x 3.0 mm). Mobile phase contained water and acetonitril with 0.025 % addition of formic acid. Separation was carried out under the gradient elution with the profile 0. - 1. min 4 % acetonitrile; 1. - 25. min 4 → 55 % acetonitrile; 25. - 30. min 4 %...
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Identification of related compounds by GC-MS
Kušnír, Jaroslav ; Vrbatová, Ivana (referee) ; Kučera, Radim (advisor)
Identification of Related Substances Using GC-MS Thesis Jaroslav Kušnír Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control A molecular weight was researched for the purpose of identifying three foreign matters, which were found in 1,3-butanediol substance during GC/FID. GC/MS technique was used for researching molecular weight. Following techniques were used to ionize the samples - electron ionization, chemical ionization using methane and isobutene reagent gases. To acquire a more stable molecular ion, different derivative reactions were tried as for example acylation. Nevertheless result were not satisfiable. Chemical ionization using isobutene reagent gas was found to be the most effective for researching molecular weight of the foreign matters. Isobutene is more sensitive reagent gas than methane and therefore a more intensive ion (M+H)+ can be found in the mass spectrum, from which it is possible to define molecular weight. Apart from researching molecular foreign matters, the best conditions for using reagent gas isobutene in GC/MS were examined. From the measuring it was found that the best conditions are during 80 kPa pressure and increased voltage by 0.4 kV from the default setting of the detector. Molecular weight of...
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Employment of separation methods in the field of drug analysis II.
Ferebauerová, Markéta ; Kastner, Petr (referee) ; Kučera, Radim (advisor)
Employment of separation methods in the field of drug analysis II Diploma Thesis Markéta Ferebauerová Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control This diploma thesis summarizes findings of both drug analysis done by gas chromatography and validation of analytical method. The mixture of glycerol, 1,3-butanediol and two other substances was studied. Specifity, linearity, precision and accuracy were studied and verified. In terms of robustness, the following parameters of the method were changed: the flow rate of carier gas, spit ratio, carier gas, stability of the sample, the temperature of detector, the temperature of injection port and the temperature of column. Further, the author demonstrate that the method is mostly influenced by the flow rate of carier gas and the temperature of column of the first part. Finally,the 24-hour stability of the sample was confirmed.
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Development of an LC-MS method for determination of new antimalarial drugs in biological matrices.
Klimeš, Jiří ; Kučera, Radim (referee) ; Kovaříková, Petra (advisor)
Artemisinin a representative of Endoperoxide class of drugs and its derivatives particularly artesunate are the most important class of antimalarial drugs used in clinical practice. They are recommended as the first-line treatment of malaria in combination with other longer-acting antimalarial drugs (lumefantrine, piperaquine). As the main skeleton of these compounds lacks UV visible or fluorescent chromophore, earlier methods of detection have used post-column on-line derivatisation or electrochemical detection in the reductive mode. However, these methods suffer from poor sensitivity and selectivity. Within this thesis the whole LC-MS method development for the analysis of artesunate and its major metabolite dihydroartemisin in biological samples from the very beginning was performed. It included tuning of ESI - triple quadrupole MS detector and optimization of chromatographic conditions, particularly mobile phase pH. Artesunate (ARST) and dihydroartemisin (DHA) were assayed in human plasma using artemisisnin as an internal standard. Different approaches of plasma sample treatment, (protein precipitation and liquid- liquid extraction) were optimized and compared. Pre-validation data for liquid-liquid extraction revealed LLOQ as 2.5 and 3.0 ng/ml for DHA and ARST, respectively using 400 μl of...
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Determination of Valproic Acid using Capillary Gas Chromatography with Mass Spectrometry Detection
Šillerová, Tereza ; Kučera, Radim (referee) ; Kastner, Petr (advisor)
Valproic acid is a chemical compound with simple structure and wide therapeutic effect. It is primarily used in treatment of epilepsy, bipolar disorder and rarely in treatment of depress. The serum levels of valproic acid have to be determined due to its narrow therapeutic window and risk of drug-drug interactions. Thus a new sensitive analytical method using capillary gas chromatography with mass spectrometric detection has been developed for determination of valproic acid levels in human serum (caprylic acid used as an internal standard). The results showed that the new method was linear within the range of 0,96 - 967,38 µmol/l, which include the therapeutic range (367 - 693 µmol/l) of valproic acid. This method was compared with formerly established fluorescence polarization immunoassay (FPIA) method for determination of valproic acid levels in human serum (FPIA) by means of the Passing-Bablok regression analysis and Bland & Altman Plot. The statistical analysis confirmed that new method is suitable for determination of levels of valproic acid in real human serum samples. The validated method has been applied to the routine analysis of patient's serum samples.
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Employment of gas chromatography in the field of drug analysis IV.
Kratochvílová, Eva ; Kovaříková, Petra (referee) ; Kučera, Radim (advisor)
Employment of gas chromatography in the field of drug analysis IV. Diploma thesis Eva Kratochvílová Charles Univerzity in Pratur, Fakulty of Pharmacy in Hradec Králové, Department of Pharmaceutical Chemistry and Drug Control Heyrovského 1203, Hradec Králové This diploma thesis deals with the validation of analytical method for impurities determination in butane-1,3-diol by gas chromatography. Determination of ideal parameters for separation- temperature on column, temperature gradient, velocity of carrier gas and split ratio, allows ideal separation of the peak butane-1,3-diol and its impurities. For sample quantification was tested method of internal standard and method of normalization. The method of normalization was then validated. Validation of method includes linearity, reproducibility, robustness, LOD and LOQ. The found method meets all parametrs. The sample stability was confirmed by series of measurements during 24 hours.
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Employment of HPLC in the field of drug analysis III.
Václavková, Jana ; Kovaříková, Petra (referee) ; Kučera, Radim (advisor)
Diploma thesis The use of HPLC in the analysis of drugs III Jana Václavková Charles Univerzity in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Chemistry and Drug Control High-performance liquid chromatography is one of the most progressive separative and analytical methods. Phases based on the oxide of zirconium with more advantageous chemical properties represent an alternative to classical stationary silica gel phases. The aim of this diploma thesis was to transfer the conditions of separation from the column ZirChrom® -PBD to the column Zirchrom® -MS and, thus, enable connection with the mass detector. During the separation, various types of buffer (diammonium hydrogen phosphate, ammonium acetate), concentrations of buffer, and constitutions of the mobile phase (solvents: acetonitrile, methanol) were used. For the separation of ondansetron and its five impurities, the following optimal conditions were found out: a mobile phase composed of acetonitrile and 5 mM ammonium acetate (pH 7), 0-4 min. (40 : 60, V/V), 4-5 min. (40→50 : 60→50, V/V), 5-21 min. (50 : 50, V/V), 21-25 min. (50→40 : 50→60, V/V). The analysis was carried out at the temperature of 40 řC and the flow rate of 0.5 mL min-1 . The detection was performed at the wavelength of 216 nm. The separation...
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Employment of HPLC in the field of Drug analysis I.
Kalafut, Peter ; Kučera, Radim (advisor) ; Kovaříková, Petra (referee)
Curcumin with it's derivates belongs to pharmacologically acting diarylheptanoids. They are obtained from the herbal rhizomes of genus Curcuma spp. (Zingiberaceae), which are widespread in tropical regions of south-east Asia. For last decades the drug has been in focus of scientists. On the human organism there have been proven many interesting effects. Therapeutically are used it's choleretic, antioxidant and antiinflammatory activities. Nowadays the interest orientates to the prevention and treatment of cancer and to the favourable influence on Alzheimer's disease. After oral administration, however, curcumin achieves the system circulation only in traces. In introduced study we developed HPLC method for the determination of curcuminoids. The most advantageous way is extracting the pigments from the herb or extract with methanol as relatively polar solvent. In the aqueous medium is practically unsoluble. The presence of three acid hydrogens exhibits in the alkaline aqueous solutions. The resultating ionisation is documented by color change from yellow to red. These conditions prejudice the stability of the substance - in part we may prevent the degradation by using the antioxidants and keeping in dark place. The analysis utilizes a reversed-phase C18 column and involves the use of an external...
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HPLC analysis of drug candidates from the group of aroylhydrazones II.
Stariat, Ján ; Kovaříková, Petra (advisor) ; Kučera, Radim (referee)
1. ABSTRACT High performance liquid chromatography (HPLC) is one of the most frequently used analytical techniques for the analysis of drugs. Although iron is a vital element, excessive amounts in the body are highly toxic. The search for highly selective and effective iron chelating agents has been mainly inspired by the need to mobilize iron from tissues that are chronically overloaded with iron. However, recent investigations focused on the possibility to use iron chelators for the treatment of many other pathologies. Salicylaldehyde isonicotinoyl hydrazone (SIH), a biocompatible iron chelator derived from aroylhydrazone, is under extensive investigation as a promising drug candidate. Besides ability to bind iron, it shows interesting pharmacological effects: antioxidative, antiproliferative, cardioprotective, antimalarical and antimicrobic. The aim of this study was to develop optimal HPLC conditions for the separation of SIH and its potential metabolites (isoniazide, acetylisoniazide, salicylaldehyde) and to apply the method to the study focused on the isolation of analytes from rabbit urine using SPE. The best chromatographic analysis was achieved on a HPLC column (Phenomenex 250 4.6 mm I. D.) packed with Prodigy 5u ODS3 100A (5 μm) as a stationary phase. The mobile phase was composed of methanol :...
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The alternative stationary phases in HPLC analysis of drugs
Holásková, Petra ; Kovaříková, Petra (referee) ; Kučera, Radim (advisor)
Rigorous thesis The Alternative HPLC Phases for Analysis of Pharmaceuticals Mgr. Petra Holásková Charles Univerzity in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Chemistry and Drug Control The solubility of silica gel at high pH is the cause for developing alternative HPLC columns based on metal oxides, such as titanium oxide, aluminium oxide, and zirconium oxide. Advantages of these columns are particularly high chemical stability and separation efficiency. In our project, zirconia-based stationary phases were tested in qualitative and quantitative analysis of doxazosine and its five impurities. Polystyrene-coated zirconia was chosen because of its low retention and appropriate selectivity. The separation was done within 16 min. Subsequently, chromatographic conditions were validated.
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