Determination of Lercanidipine Hydrochloride and Its Impurities in Tablets

The reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed for determination of lercanidipine hydrochloride and its synthetic impurities, degradation and oxidative products in Carmen^® tablets. The best separation was performed on Zorbax SB C18 column, 250 x 4.6 mm, particle size 5 m. Acetonitrile-water-triethylamine 55:44.8:0.2 (v/v/v) was used as a mobile phase with flow rate 1 mL min^–1. pH was adjusted to 3.0 with orthophosphoric acid. UV detection was performed at 240 nm. Duration of chromatographic run was about 12 min for six examined compounds. The chromatographic conditions for the determination of lercanidipine hydrochloride and its related substances were the same, but the concentration of lercanidipine hydrochloride was 0.03 mg mL^–1 for assay and 0.3 mg mL^–1 for related substances. The validation of the method performance characteristics (figures of merits, quality of parameters) was established to be adequate for the intended use. The evaluation of number of parameters, such as selectivity, linearity, accuracy, specificity, precision (repetability and reproducibility), sensitivity and detection and determination limits is entailed.Acknowledgements This work was supported by the Institute of Pharmacy of Serbia, Belgrade and by the Ministry for Science, Technology and Development of Serbia, Contact: 1458     

Spectrophotometric assay of cephalosporins in pharmaceutical products,using chromotrope 2B and chromotrope 2R

A simple, rapid and sensitive Spectrophotometric method is proposed for the determination of cephadroxil (I), cephalexin (II) and cephradine (III). The method is based on ion-pair complex formation between these derivatives and Chromotrope 2B (C2B) or Chromotrope 2R (C2R), to give a highly coloured radical anion. The coloured products are quantified spectrophotometrically at 542 and 564 nm for C2B and C2R, respectively. The optimization of the experimental conditions is described. The method has been used for the determination of 0.4–15, 0.4–14 and 0.4–18 g/ml of drugs I, II and III, respectively. The accuracy of the method is indicated by the excellent recovery (100.0±1.7%) and the precision is supported by the low relative standard deviations 1.5%. The sensitivity of the method is discussed and the results are compared with the official method. The interference from common degradation products and excipients was also studied. The proposed method was applied successfully to the determination of the different cephalosporins in dosage forms, with good precision and accuracy. The results were compared with those given by the official B.P. 1993 method.     

Kinetic determination of trace levels of selenium(IV) and total selenium by Nile Blue A/hydrogen peroxide method

A kinetic method for the determination of selenium(IV) traces is proposed, based on its inhibitory action on the oxidation of Nile Blue A by hydrogen peroxide in phosphate buffer (pH 10.5). A linear dependence was established between the rate of the proposed indicator reaction and selenium concentration in the range 9.5 × 10^–2-1.58 ng cm^–3. The experimental conditions of maximal selenium effect were established. Selenium, determined by the tangent method, was determined at concentrations over the range 0.22–1.26 ng cm^–3, with relative standard deviations up to 4.5%. The reaction rate was followed spectrophotometrically. The effect of foreign ions on the accuracy of this method was also investigated. The method was applied to the determination of selenium in pharmaceutical preparations and wheat flour.     

中药血清药理学研究金银花的抑菌活性

采用最低抑菌浓度(MIC)测定方法和抑菌活性试验,考察不同产地的金银花以及含药血清的抑菌效果。试验结果为:含药血清对大肠杆菌和金黄色葡萄球菌的MIC分别为0.5μg绿原酸/mL和0.25μg绿原酸/mL;含药血清抑菌活性为高敏。     

Determination of pefloxacin in serum and pharmaceutical forms by derivative spectrophotometry

A method for the direct determination of pefloxacin in serum and pharmaceutical forms (tablets and ampoules) has been developed, based on the use of second-order derivative ultraviolet spectra. Spectrophotometric assay of pefloxacin in tablets and ampoules was carried out in 0.1 mol/L NaOH, while in serum it was performed in 0.1 mol/L NaOH with the addition of sodium dodecylsulfate, in 337–347 nm wavelength range. Linear calibration curves were obtained in the concentration ranges 2–30g/mL pefloxacin for tablets and ampoules and 0.12–5 g/ mL for serum samples. Relative error of determination, as criterion for accuracy, was less than 1%, while the precision was better than 4 ng/ml. The minimum detectable concentration of pefloxacin in serum was 15 ng/mL.     

Profiling analysis of oligosaccharides in antibody pharmaceuticals by capillary electrophoresis

Carbohydrate chains in glycoprotein pharmaceuticals have important roles for the expression of their biological activities. Therefore, development of an assessment method for the carbohydrate chains is an important parameter for quality control of glycoprotein pharmaceuticals such as newly developed therapeutic antibodies. In this report, we applied capillary electrophoresis with laser-induced fluorescence detection to the analysis of carbohydrate chains after releasing with glycoamidase followed by derivatization with 3-aminobenzoic acid. We found that four major oligosaccharides present in antibody pharmaceuticals were successfully separated with good resolution. The present method showed good precision in both migration times and relative peak areas, and gave comparable accuracy with that using a derivatization method with 8-aminopyrene-1,3,6-trisulfonate.     

Applications of Thermal Analysis and Coupled Techniques in Pharmaceutical Industry

Thermal analysis methods are well-established techniques in research laboratories of pharmaceutical industry. The robustness and sensitivity of instrumentation, the introduction of automation and of reliable software according to the industrial needs widened considerably the areas of applications in the last decade. Calibration of instruments and validation of results follow the state of the art of cGMP as for other analytical techniques. Thermal analysis techniques are especially useful for the study of the behavior of the poly-phasic systems drug substances and excipients and find a unique place for new delivery systems. Since change of temperature and moisture occur by processing and storage, changes of the solid state may have a considerable effect on activity, toxicity and stability of compounds. Current requirements of the International Conference of Harmonisation for the characterization and the quantitation of polymorphism in new entities re-enforce the position of thermal analysis techniques. This challenging task needs the use of complementary methods. Combined techniques and microcalorimetry demonstrate their advantages. This article reviews the current use of thermal analysis and combined techniques in research and development and in production. The advantage of commercially coupled techniques to thermogravimetry is emphasized with some examples. This revised version was published online in August 2006 with corrections to the Cover Date.     

Multi-Step Continuous-Flow Organic Synthesis: Opportunities and Challenges

Continuous-flow multi-step synthesis takes the advantages of microchannel flow chemistry and may transform the conventional multi-step organic synthesis by using integrated synthetic systems. To realize the goal, however, innovative chemical methods and techniques are urgently required to meet the significant remaining challenges. In the past few years, by using green reactions, telescoped chemical design, and/or novel in-line separation techniques, major and rapid advancement has been made in this direction. This minireview summarizes the most recent reports (2017–2020) on continuous-flow synthesis of functional molecules. Notably, several complex active pharmaceutical ingredients (APIs) have been prepared by the continuous-flow approach. Key technologies to the successes and remaining challenges are discussed. These results exemplified the feasibility of using modern continuous-flow chemistry for complex synthetic targets, and bode well for the future development of integrated, automated artificial synthetic systems.     

Practical guide for selection of 1H qNMR acquisition and processing parameters confirmed by automated spectra evaluation

In our recent paper, a new technique for automated spectra integration and quality control of the acquired results in qNMR was developed and validated (Monakhova & Diehl, Magn. Res. Chem. 2017, doi: 10.1002/mrc.4591 ). The present study is focused on the influence of acquisition and postacquisition parameters on the developed automated routine in particular, and on the quantitative NMR (qNMR) results in general, which has not been undertaken previously in a systematic and automated manner. Results are presented for a number of model mixtures and authentic pharmaceutical products measured on 500‐ and 600‐MHz NMR spectrometers. The influence of the most important acquisition (spectral width, transmitter [frequency] offset, number of scans, and time domain) and processing (size of real spectrum, deconvolution, Gaussian window multiplication, and line broadening) parameters for qNMR was automatically investigated. Moderate modification of the majority of the investigated parameters from default instrument settings within evaluated ranges does not significantly affect the trueness and precision of the qNMR. Lite Gaussian window multiplication resulted in accuracy improvement of the qNMR output and is recommended for routine measurements. In general, given that the acquisition and processing parameters were selected based on the presented guidelines, automated qNMR analysis can be employed for reproducible high‐precision concentration measurements in practice.     

Simultaneous Determination of Acetaminophen and Phenobarbital in Suppositories by Partial Least-Squares Spectrophotometric Calibration

Abstract

The use of partial least-squares spectrophotometric calibration for the simultaneous determination of suppositories in a multicomponent formulation is presented. This method is applied to the deternination of acetaminophen and phenobarbital in suppository preparations. The results show that these components in a molar ratio of about 61:1 in suppositories have been determined simultaneously with high precision.