Application of the Principles of Green Chemistry for the Development of a New and Sensitive Method for Analysis of Ertapenem Sodium by Capillary Electrophoresis.

An innovative method is validated for the analysis of ertapenem sodium by capillary electrophoresis using potassium phosphate buffer 10 mM pH 7 and 15 kV voltage, in the concentration range of 70 to 120 µg mL-1. Ertapenem had a migration time of 3.15 minutes and the linearity curve was y = 2281.7 x - 24495 with a R2 = 0.9994. Thus, we propose a routine analysis method that meets the principles of green analytical chemistry for the routine analysis of ertapenem sodium by capillary electrophoresis.

Venlafaxine Determination in Pharmaceutical Formulation and Serum by Ion-Selective Electrodes.

BACKGROUND: The application of an ion selective technique for the determination of analyte concentrations is considered one of the most economical techniques for quality control purposes. OBJECTIVE: To elaborate and investigate the construction and general performance characteristics of potentiometric PVC membrane sensors for venlafaxine cation (Ven+). METHOD: The sensors are based on the use of the ion association complexes of the venlafaxine cation with phosphotungstate (PT) and silicotungstate (ST) counter anions as ion exchange sites in the plasticized PVC matrix. They are characterized by potentiometric and conductimetric measurements, performed under various conditions. RESULTS: The electrodes showed a fast (response time around 15 s), stable (life span 45 days) and linear (r2 0.995) response for venlafaxine over the concentration range of 5x10-5 - 1x10-2 M venlafaxine hydrochloride. The solubility product of the ion pair and the formation of the precipitation reaction leading to the ion pair, were determined conductimetrically. The electrodes were found to be very selective, precise (RSD < 1%) and applicable to the potentiometric determination of venlafaxine hydrochloride in pure solutions or in pharmaceutical preparation and in biological fluid (serum), without any interference. Validation of the method shows the suitability of the proposed electrodes for use in the quality assessment of venlafaxine hydrochloride. CONCLUSION: Using only a pH meter in combination with the selective electrodes, drug substance or drug product could be determined accurately in a few seconds. In addition, the in-house made electrodes were tested to monitor venlafaxine in serum. Acceptable results were achieved using the standard addition technique.

Characterization of impurities in sodium cromoglycate drug substance and eye drops using LC-ESI-ion trap MS and LC-ESI-QTOF MS.

As requested by regulatory authorities, impurity profiling is an important issue of quality control. In this work, a simple and sensitive liquid chromatographic (LC) method compatible with mass spectrometry (MS) was developed to study related substances and degradation products in sodium cromoglycate drug substance and eye drops. The method used a Sunfire column (4.6mm×150mm, 3.5µm). Mobile phase A consisted of 10mM ammonium formate and mobile phase B was acetonitrile. Linear gradient elution with a post-run time of 8min was performed as follows: 0-30min, 3% B to 50% B; 30-35min, 50% B. The flow rate was set at 1.0mL/min. Degradation experiments were performed to check the stability indicating properties of the developed method. Based on MSn spectral data and exact mass measurements, the chemical structures of 2 unknown impurities and 6 unknown degradation products were characterized, including impurity C listed in the European Pharmacopoeia as unknown structure. In addition, a plausible mechanism for the formation of the degradation products was also proposed.

Thermal desorption-Gas chromatographic methodology for the determination of residual solvents in mesoporous silica.

In this work, thermal desorption-gas chromatography-flame ionization detection (TD-GC-FID) was adapted to enable the determination of residual solvents (RS) in mesoporous silica (MPSi). MPSi is often utilized in various pharmaceutical formulations or drug delivery systems and the accurate determination of RS is an important part of pharmaceutical quality control. Seven commonly used solvents (methanol, ethanol, acetone, isopropanol, dichloromethane, tetrahydrofuran and hexafluoroisopropanol) were evaluated in combination with 3 types of MPSi having pore sizes of 2-3, 15 and 25nm. Validation results showed general recovery values >98% and good linearity over the concentration ranges studied. The limits of detection (LOD) and limits of quantification (LOQ) for the different solvents ranged from 0.03 to 0.08µg and from 0.1 to 0.2µg per tube, respectively. Verification of the accuracy of the TD method was investigated by using an alternative method based on complete dissolution of MPSi in hydrofluoric acid (HF) followed by full evaporation headspace-GC (HS-GC). The results obtained from both procedures were not statistically different (p>0.05) when applied to actual experimental drug samples consisting of itraconazole loaded on MPSi.

Recent advances in CE-mediated microanalysis for enzyme study.

This review gives an overview of the recent developments and applications in the use of CE-mediated microanalysis for enzyme studies. The period covers mid-2011 until mid-2013. Both off-line and in-line enzyme assays with their applications using CE are described in this article. For the in-capillary enzyme reaction, the techniques using electrophoretically mediated microanalysis (EMMA) as well as immobilized enzyme reactor (IMER) are discussed. The applications include the evaluation of enzyme activity, enzyme kinetics, enzyme inhibition, screening of enzyme inhibitors, and the study of enzyme-mediated drug metabolism.

Development and validation of a capillary electrophoresis method for the determination of escitalopram and sensitive quantification of its enantiomeric impurity in formulations.

A rapid capillary zone electrophoresis method has been developed capable of quantifying 0.05% of R-enantiomer and assaying the main component in escitalopram formulations. Many parameters influencing enantioseparation were investigated, which include chiral selectors, buffer composition and pH, applied voltage, capillary length, temperature, and rinsing procedure. Optimal separation conditions were obtained by using a 25 mM phosphate buffer at pH 7.0, containing 1.6% (w/v) sulfated-ß-cyclodextrin with short-end injection at 0.5 psi for 5 s. Online UV detection was performed at 205 nm. A voltage of -20 kV was applied and the capillary temperature was kept at 25°C. Separation was achieved in less than 2 min. The method was further validated, including robustness, stability of the solution, selectivity, linearity (escitalopram from 0.25 µg/mL to 600 µg/mL, y = 1528.3 × +1812.9; R² = 0.9999), LOD and LOQ (0.08 and 0.25 µg/mL, respectively), precision and accuracy. The proposed method was then applied to the quality control of the bulk sample and tablets of escitalopram (10 mg).

Recent developments and applications of EMMA in enzymatic and derivatization reactions.

This review provides systematic coverage of examples in the field of in-capillary electrophorecially mediated microanalysis (EMMA). The recent developments and applications in the time period up to mid 2011 have been described, as well as relevant older papers. The basic principles and modes of in-capillary assays have been demonstrated. An overview is also given of the various injection, separation and detection modes implemented in combination with EMMA. The review is presented in two parts mainly dealing with (i) enzymatic and (ii) derivatization or chemical reactions. Finally, the future trends of CE in performing and monitoring reactions have been drawn.

Micellar electrokinetic chromatography method development for determination of impurities in ritonavir.

Ritonavir is a synthetic peptidomimetic human immunodeficiency virus (HIV) protease inhibitor employed in the treatment of AIDS since 1996. Synthetic precursors are potential impurities in the final product. In the present work a micellar electrokinetic chromatography (MEKC) method for the separation of Ritonavir from three available synthetic precursors was developed. The optimized separation is performed in a background electrolyte composed of sodium tetraborate (pH 9.6; 15mM) containing sodium dodecylsulfate (30mM) and acetonitrile (18%, v/v). Mass spectrometry was used to confirm the identity of the tested substances. Good repeatability was observed for migration time (RSD about 0.4%) and peak area (RSD about 0.8%). The limits of detection (LOD) obtained allow the determination of two of the impurities at levels as low as 0.005% m/m, and one at a level of 0.3% m/m.

Investigation of degradation products in a topical gel containing erythromycin and benzoyl peroxide by liquid chromatography-mass spectrometry.

Benzamycin, combining benzoyl peroxide and erythromycin, is a topical gel used in the treatment of acne vulgaris. Because of the reactivity of benzoyl peroxide, preparations containing both erythromycin and benzoyl peroxide might be unstable and degradation products could be formed. To investigate and identify these latter products, a gradient-based liquid chromatographic method using volatile mobile phase constituents was developed. Mass spectrometry data were acquired on solutions containing erythromycin and benzoyl peroxide and on freshly prepared, 2-month-old and 18-month-old samples of Benzamycin. With the reference spectra as interpretative templates, it was concluded that erythromycin undergoes oxidation, followed by benzoylation.

Mass spectrometric study to characterize thioisoindole derivatives of aminoglycoside antibiotics.

Aminoglycoside antibiotics are widely used to treat serious Gram-negative and Gram-positive bacterial infections. The lack of a UV chromophore presents a problem in the analysis of aminoglycosides. Derivatization with 1,2-phthalic dicarboxaldehyde (OPA) in the presence of a thiol made it possible to introduce a UV chromophoric thioisoindole moiety. A qualitative mass spectrometry study was carried out to confirm the molecular identity of the products formed. The conditions described earlier to derivatize gentamicin and kanamycin yielded products in which all primary amino groups are fully derivatized. On the other hand, with tobramycin and amikacin, there was also formation of incompletely derivatized products that contained one thioisoindole group less than the fully derivatized product. This study has therefore brought an additional insight into the nature of the OPA-aminoglycoside derivatives studied.