Bilal Yilmaz

Gas chromatography–mass spectrometry method for determination of metoprolol in the patients with hypertension

A sensitive and efficient method was developed for determination of metoprolol in human plasma by gas chromatography-mass spectrometry (GC-MS). Metoprolol and atenolol (internal standard, IS) were extracted from human plasma with a mixture of ethylacetate and diethylether at basic pH with liquid-liquid extraction. Calibration curves were linear over the concentration range 15-500 ng/ml. Intra- and inter-day precision values for metoprolol in human plasma were less than 6.4, and accuracy (relative error) was better than 8.8%. The analytical recovery of metoprolol from human plasma averaged 91.20%. The limits of detection (LOD) and quantification (LOQ) of metoprolol were 5.0 and 15 ng/ml, respectively. Also the developed and validated GC-MS method was successfully applied to three patients with hypertension who had been given an oral tablet of 100mg metoprolol.

Determination of metoprolol in human plasma and urine by high-performance liquid chromatography with fluorescence detection.

A simple, specific and sensitive HPLC method has been developed for the determination of metoprolol in human plasma and urine. Separation of metoprolol and atenolol (internal standard) was achieved on an Ace C(18) column (5 microm, 250 mm x 4.6 mm id) using fluorescence detection with lambda(ex)=276 nm and lambda(em)=296 nm. The mobile phase consists of methanol-water (50:50, v/v) containing 0.1% TFA. The analysis was performed in less than 10 min with a flow rate of 1 mL/min. The assay was linear over the concentration range of 3-200 and 5-300 ng/mL for plasma and urine, respectively. The LOD were 1.0 and 1.5 ng/mL for plasma and urine, respectively. The LOQ were 3.0 and 5.0 ng/mL for plasma and urine, respectively. The extraction recoveries were found to be 95.6 +/- 1.53 and 96.4 +/- 1.75% for plasma and urine, respectively. Also, the method was successfully applied to three patients with hypertension who had been given an oral tablet of 100 mg metoprolol.

Simultaneous determination of gemcitabine and its metabolite in human plasma by high-performance liquid chromatography

Gemcitabine (dFdC) is a pyrimidine antimetabolite with broad spectrum activity against tumors. In this paper, a normal-phase high-performance liquid chromatographic method was developed for the determination of the parent drug (dFdC) and its metabolite (dFdU) in human plasma. The described sample preparation procedure for determination of dFdC and dFdU is rapid, sensitive, reproducible and simple. The linear regression equations obtained by least square regression method, were area under the curve=0.0371 concentration (ng ml(-1))+192.53 and 1.05.10(-4) concentration (ng ml(-1))-1.2693 for dFdC and dFdU, respectively. The assay for dFdC and dFdU described in the present report has been applied to plasma samples from a bladder cancer patient.

Determination of diclofenac in pharmaceutical preparations by voltammetry and gas chromatography methods

Rapid, sensitive and specific methods were developed for the determination of diclofenac in pharmaceutical preparations by linear sweep voltammetry (LSV) and gas chromatography (GC) with mass spectrometry (MS) detection. The linearity was established over the concentration range of 5–35 μg/mL for LSV and 0.25–5 μg/mL for GC–MS method. The intra- and inter-day relative standard deviation (RSD) was less than 4.39% and 4.62% for LSV and GC–MS, respectively. Limits of quantification (LOQ) were determined as 4.8 and 0.15 μg/mL for LSV and GC–MS, respectively. No interference was found from tablet excipients at the selected assay conditions. The methods were applied for the quality control of commercial diclofenac dosage forms to quantify the drug and to check the formulation content uniformity.

Determination of naproxen in human plasma by GC–MS

This paper describes a GC-MS method for the determination of naproxen in human plasma. Naproxen and internal standard ibuprofen were extracted from plasma using a liquid-liquid extraction method. Derivatization was carried out using N-methyl-N-(trimethylsilyl)trifluoroacetamide. The calibration curve was linear between the concentration range of 0.10-5.0 μg/mL. Intra- and interday precision values for naproxen in plasma were <5.14, and accuracy (relative error) was better than 4.67%. The extraction recoveries of naproxen from human plasma were between 93.0 and 98.9%. The LOD and LOQ of naproxen were 0.03 and 0.10 μg/mL, respectively. Also, this assay was applied to determine the pharmacokinetic parameters of naproxen in six healthy Turkish volunteers who had been given 220 mg naproxen.

HPLC method for determination of atenolol in human plasma and application to a pharmacokinetic study in Turkey.

This paper describes a high-performance liquid chromatography method for the determination of atenolol in human plasma. Atenolol and the internal standard, metoprolol, were extracted from plasma by using a liquid-liquid extraction method. The method was developed on an Ace C18 reverse-phase column using a mobile phase of methanol-water (50:50, v/v) containing 0.1% trifluoroacetic acid. The calibration curve was linear within the concentration range of 5-150 ng/mL. Intra-day and inter-day precision values for atenolol in plasma were less than 6.1, and accuracy (relative error) was better than 5.5%. The mean recovery of atenolol was 98.4% for plasma. The limits of detection and quantification of atenolol were 1.5 and 5 ng/mL, respectively. Also, this assay was successfully applied to six patients with hypertension who had been given an oral tablet of 50 mg atenolol.

Determination of Insulin in Humans with Insulin-Dependent Diabetes Mellitus Patients by HPLC with Diode Array Detection

A simple and reliable high-performance liquid chromatographic method with diode array detection has been developed and validated for the determination of insulin in human plasma. A good chromatographic separation was achieved on a C18 column with a mobile phase consisting of acetonitrile and 0.2M sodium sulfate (pH 2.4), 25:75 (v/v). Its flow rate was 1.2 mL/min. Calibration curve was linear within the concentration range of 0.15-25 µg/mL. Intra-day and inter-day relative standard deviations for insulin in human plasma were less than 6.3 and 8.5%, respectively. The limits of detection and quantification of insulin were 0.10 and 0.15 µg/mL, respectively. Also, this assay was applied to determine the pharmacokinetic parameters of insulin in eight insulin-dependent diabetes mellitus patients after subcutaneous injection of 25 IU of Actrapid HM.

QUANTITATION OF 17 β-ESTRADIOL IN RABBIT PLASMA BY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY WITH FLUORESCENCE DETECTION

A new method was developed for the determination of 17 β-estradiol in rabbit plasma by reversed-phase high performance liquid chromatography (RP-HPLC) with fluorescence (FL) detection. The method employed one-step extraction of 17 β-estradiol from plasma matrix with a mixture of water and ethylacetate (1.9:5, v/v) using estriol as an internal standard. The mobile phase consisted of a mixture of metanol and water (70:30, v/v) flowing at a flow rate of 1.0 mL min−1. Calibration curve was linear between concentration range of 125–6000 ng mL−1. Average recovery of 17 β-estradiol and the internal standard from the biological matrix was more than 94.9 and 92.5%, respectively. The intra-day and inter-day precision and accuracy were between 3.74–8.12 and 3.72–8.80%, respectively. Also, the method was successfully applied to determine of 17 β-estradiol in New Zealand white rabbits.

Enhanced removal of basic violet 10 by heterogeneous sono-Fenton process using magnetite nanoparticles

The removal of basic violet 10 (BV10), which is known as a cationic dye, from aqueous solution was studied by employing a heterogeneous sono-Fenton process over the nano-sized magnetite (Fe3O4) which had been prepared by the milling of magnetite mineral using a high-energy planetary ball milling process. The magnetite samples were characterized using the X-ray diffraction (XRD), high resolution scanning electron microscopy (HR-SEM), energy-dispersive X-ray spectroscopy (EDX), Brunauer-Emmett-Teller (BET), Fourier transform infrared spectroscopy (FTIR), and inductively couple plasma mass spectrometer (ICP-MS). It was found that the catalytic activity of the ball-milled magnetite sample was enhanced along with the improvement in its physicochemical properties; also, the ball-milled magnetite of 6 h displayed the highest catalytic activity in BV10 removal by the heterogeneous sono-Fenton process as compared with that for 4 h (66.12% after 120 min) and 2 h (48% after 120 min).The effect of operational parameters, namely, pH solution, catalyst dosage, the initial H2O2 concentration, ultrasonic power and the initial BV10 concentration, on the removal efficiency (RE%) of BV10 was investigated. The optimum conditions for the BV10 RE% were: the pH value of 3, the catalyst dosage of 1.5 g L-1, the initial H2O2 concentration of 36 mM, the ultrasonic power of 450 W L-1, and the initial BV10 concentration of 30 mg L-1. The RE% of BV10 was 75.94% at these conditions after the reaction time of 120 min. The trapping experiments revealed that OH radicals were the dominant oxidative species, but O2-/HO2 radicals also had a partial role in the removal of BV10.The reusability of the magnetite nanoparticles revealed about 28% decrease in the removal efficiency within five consecutive runs. The results obtained through GC-MS analysis also confirmed the efficient removal of BV10 molecules in the aqueous solution during the process.

Preparation of magnetite nanoparticles by high-energy planetary ball mill and its application for ciprofloxacin degradation through heterogeneous Fenton process

In this study, the heterogeneous Fenton oxidation of ciprofloxacin (CIP) in an aqueous solution was examined over the nano-sized magnetite (Fe3O4) as a catalyst supplied through high-energy planetary ball milling process. To characterize the magnetite samples after and before ball milling operation, the X-ray diffraction (XRD), High-resolution scanning electron microscopy (HR-SEM), energy-dispersive X-ray spectroscopy (EDX), Brunauer-Emmett-Teller (BET) and Fourier transform infrared spectroscopy (FTIR) analysis were applied. The catalytic properties of the magnetite were considerably improved because of the enhancement in its physical properties, resulted from milling process. The findings also indicated that 6 h ball-milled magnetite demonstrated better properties for elimination of CIP of about 89% following 120 min reaction at optimal conditions of H2O2 12 mM, Fe3O4 1.75 g L-1, CIP 10 mg L-1 and pH 3.0. The effects of various operational parameters, including the initial pH of the solution, H2O2 initial concentration, catalyst dosage, milling time and CIP initial concentration was investigated. Application of organic and inorganic scavengers considerably decreased the CIP removal efficiency. Correspondingly, with respect to the leached iron values at pH 3, it was concluded that CIP elimination was mainly occurred through heterogeneous Fenton procedure. This process included the adsorption and oxidation phases in which the hydroxyl radicals (OH) played a significant role. GC-MS analysis was used for recording of the generated intermediates of the CIP removal in the course of heterogeneous Fenton process.