Duygu Yeniceli

A simple and sensitive LC–ESI-MS (ion trap) method for the determination of bupropion and its major metabolite, hydroxybupropion in rat plasma and brain microdialysates

A specific and highly sensitive liquid chromatography-electrospray mass spectrometry (LC-ESI-MS) method for the direct determination of bupropion (BUP) and its main metabolite hydroxybupropion (HBUP) in rat plasma and brain microdialysate has been developed and validated. The analysis was performed on a Bonus RP C18 (100 mm × 2.1mm i.d., 3.5 μm particles) column using gradient elution with the mobile phase consisting of acetonitrile and ammonium formate buffer (10mM, pH 4). Plasma samples were analyzed after a simple, one-step protein precipitation clean-up with trichloroacetic acid (TCA), however clean-up for microdialysis samples was not necessary, enabling direct injection of the samples into the LC-ESI-MS system. Signals of the compounds were monitored under the multiple reaction monitoring (MRM) mode of the LC-ESI-MS (ion trap) for quantification. The precursor to product ion transitions of m/z 240-184 and m/z 256-238 were used to measure BUP and HBUP, respectively. The method was validated in both plasma and microdialysate samples, and the obtained lower limit of quantification (LLOQ) was 1.5 ng mL(-1) for BUP and HBUP in both matrices. The intra- and inter-day assay variability was less than 15% for both analytes. This LC-ESI-MS method provided simple sampling, rapid clean-up and short analysis time (<9 min), applicable to the routine therapeutic monitoring and pharmacokinetic studies of BUP and HBUP.

A validated thin-layer chromatographic method for analysis of bupropion hydrochloride in a pharmaceutical dosage form

A simple and sensitive thin-layer chromatographic method has been established for analysis of bupropion hydrochloride in pharmaceutical tablets. Chromatography on silica gel 60 F254 plates with 30:10:1 (v/v) ethanol-chloroform-glacial acetic acid as mobile phase furnished compact spots at RF 0.56 ± 0.01. Densitometric analysis was performed at 254 nm. To show the specificity of the method bupropion hydrochloride was subjected to acid and alkaline hydrolysis, oxidation, photodegradation, and dry and wet heat treatment; peaks of degradation products were well resolved from that of the pure drug. Linear regression analysis revealed a good linear relationship between peak area and amount of bupropion hydrochloride in the range 200–1000 ng per band. The limits of detection and quantitation were 11.45 and 34.71 ng per band, respectively. The method was validated, in accordance with ICH guidelines, for precision, accuracy, robustness, and ruggedness. The intra-day and interday repeatability of the method, as RSD, was approximately 1–2%, showing method precision was sufficient. Method recovery was between 102.07 and 104.58% and between 97.20 and 102.19% for quality-control standards and for bupropion hydrochloride in a synthetic mixture, respectively. Statistical comparison of results with those obtained from HPLC analysis proved the method is reproducible and enables selective analysis of bupropion hydrochloride in pharmaceuticals. Because the method could effectively separate the drug from its degradation products, it can be regarded as stability indicating.

Determination of Leflunomide in Pharmaceutical Tablets by Flow‐Injection Analysis

Abstract A flow injection analysis (FIA) of leflunomide using UV‐detection is described, in this study. The most suitable carrier solvent was found to be an aqueous solution of ethanol (25%, v/v). Leflunomide was determined at the optimum conditions, such as flow rate of 0.8 mL · min−1 and detection wavelength of 260 nm. The method has been validated and linearity was examined in the range of 2.75×10−6−1.10×10−4 M. The limit of detection (LOD) and quantitation (LOQ) were calculated to be 2.60×10−7 M (S/N=3.3) and 7.87×10−7 M (S/N=10), respectively. The application of the proposed method has been performed in pharmaceutical tablets of leflunomide and excellent results were obtained. The results were compared with those obtained from UV‐spectrophotometry. Insignificant difference was found between the methods. As a result, the FIA method for the determination of leflunomide in pharmaceutical tablets can be proposed as a precise, accurate, sensitive, and cheap method for routine analysis laboratories.

A SIMPLE AND SPECIFIC HPLC METHOD FOR THE DETERMINATION OF ATOMOXETINE IN PHARMACEUTICALS AND HUMAN PLASMA

A liquid chromatographic method has been described for the determination of atomoxetine in pharmaceuticals and human plasma. Plasma samples were analyzed after a simple, one step protein precipitation with methanol, and chromatographic separation of atomoxetine and carbamazepine (internal standard) was carried out using the optimum mobile phase of a methanol/acetonitrile/phosphate buffer (10 mM, pH 3.0) (35:15:50, v/v/v). Limit of quantification values were 45.2 and 49.5 ng/mL for atomoxetine in the mobile phase and human plasma, respectively. Fully validated method is reproducible and selective for the determination of atomoxetine in pharmaceuticals and human plasma.

Development and validation of a simple and efficient HPLC method for the determination of zonisamide in pharmaceuticals and human plasma

A simple and efficient liquid chromatographic method has been developed and validated for the determination of zonisamide in pharmaceuticals and human plasma. Plasma samples are analyzed after one step protein precipitation with methanol, and chromatographic separation of zonisamide and chloramphenicol (internal standard) is carried out using a C18 column and the optimum mobile phase of acetonitrile/methanol/distilled water (20: 10: 70, v/v/v). The method is validated in both mobile phase and human plasma, and the obtained limits of quantification values are 0.099 and 0.12 μg/mL in mobile phase and human plasma, respectively. Fully validated method is reproducible and selective for the determination of zonisamide in pharmaceuticals and human plasma.