Determination of Bortezomib in API Samples Using HPLC: Assessment of Enantiomeric and Diastereomeric Impurities.

A new, normal phase high performance liquid chromatography (NP-HPLC) method was developed for separation of Bortezomib (BZB) enantiomers and quantitative determination of (1S,2R)-enantiomer of BZB in active pharmaceutical ingredient (API) samples. The developed method was validated based on International Conference on Harmonisation (ICH) guidelines and it was proved to be accurate, precise and robust. The obtained resolution (RS) between the enantiomers was more than 2. The calibration curve for (1S,2R)-enantiomer was found to be linear in the concentration range of 0.24-5.36 mg/L with regression coefficient (R2) of 0.9998. Additionally, the limit of detection (LOD) and limit of quantification (LOQ) were 0.052 and 0.16 mg/L, respectively. Also, in this study, a precise, sensitive and robust gradient reversed-phase HPLC (RP-HPLC) method was developed and validated for determination of BZB in API samples. The detector response was linear over the concentration range of 0.26-1110.5 mg/L. The values of R2, LOD and LOQ were 0.9999, 0.084 and 0.25 mg/L, respectively. For both NP-HPLC and RP-HPLC methods, all of the RSD (%) values obtained in the precision study were <1.0%. System suitability parameters in terms of tailing factor (TF), number of theoretical plates (N) and RS were TF < 2.0, N > 2,000 and RS > 2.0. The performance of two common integration methods of valley to valley and drop perpendicular for drawing the baseline between two adjacent peaks were investigated for the determination of diastereomeric impurity (Imp-D) in the BZB-API samples. The results showed that the valley to valley method outperform the drop perpendicular method for calculation of Imp-D peak areas. Therefore, valley to valley method was chosen for peak integration.

Electrochemical determination of atorvastatin on nano-scaled polypyrrole film.

Pyrrole was electro-polymerized on the surface of the glassy carbon electrode (GCE) coated with a thin film of carbon nanomaterials, including carbon nanotubes (CNTs), carbon nanoparticles (CNPs), nanodiamond-graphite (NDG) or graphite nanopowder (GNP). Morphology, thickness, stability and loading of the polypyrrole (PPY) film were significantly affected by the structure and morphology of the sub-layer of carbon nanomaterials. Electrochemical oxidation of atorvastatin (ATOR) was investigated. Under the optimized conditions, a significant increase in the peak current (compared to other modified electrodes and bare GCE) and a negative shift in the peak potential (compared to bare GCE) were observed on the surface of the CNTs/PPY modified electrode. The electrode was able to completely resolve the voltammetric response of ATOR from potentially interfering species, e.g. ascorbic acid (AA), uric acid (UA) and dopamine (DA) which are present in many biological systems. Two linear dynamic ranges of 0.005-0.1µM and 0.1-1µM with a detection limit of 1.5nM and a sensitivity of 267.68 (±1.26) µA/µM were obtained for ATOR from linear sweep voltammetry (LSV) measurements. The modified electrode with high sensitivity, stability and good reproducibility showed promising results for determination of the ATOR concentration in pharmaceutical and clinical preparations.

Electrochemical determination of clozapine on MWCNTs/new coccine doped PPY modified GCE: an experimental design approach.

The electrooxidation of clozapine (CLZ) was studied on the surface of a glassy carbon electrode (GCE) modified with a thin film of multiwalled carbon nanotubes (MWCNTs)/new coccine (NC) doped polypyrrole (PPY) by using linear sweep voltammetry (LSV). The pH of the supporting electrolyte (D), drop size of the cast MWCNTs suspension (E) and accumulation time of CLZ on the surface of modified electrode (F) was considered as effective experimental factors and the oxidation peak current of CLZ was selected as the response. By using factorial-based response-surface methodology, the optimum values of factors were obtained as 5.44, 10 µL and 300 s for D, E and F respectively. Under the optimized conditions, a significant increase (~14 times) was observed in the anodic peak current of CLZ on the surface of the modified electrode relative to the bare GCE. Oxidation peak currents increased linearly with CLZ concentration in the range of 0.01-5.00 µM with a detection limit of 3.00 nM. The RSD value for the peak current of CLZ was obtained as 4.5%. The modified electrode with high sensitivity, stability and good reproducibility was used for the determination of CLZ concentration in pharmaceutical and clinical preparations with satisfactory results.