Use of a Single Capillary Electrophoresis Method as a Routine Identity Test for Batch Release of a Range of Pharmaceutical Products

Two independent and orthogonal analytical methods are required when performing identity testing of pharmaceutical products during routine release testing. A microemulsion electrokinetic chromatography method has been developed and validated for routine use as an identity test to release various pharmaceutical products including tablets, capsules and creams. Implementation of the method involved optimisation of parameters to achieve reliable routine operation. Rinsing procedures, in particular, were found to be essential to obtain consistent profiles and migration times. The method has replaced, and offers the potential to replace, a number of methods including HPLC and IR due to the considerable cost and time savings obtained through its use. This method has been successfully approved by the US FDA as a part of 2 New Drug Applications, is registered in Japan, and is in routine QA use within a factory environment.     

Application of MELC and MEEKC for the Analysis of Paracetamol and Related Impurities in Suppositories

Rapid MELC and MEEKC methods were developed for paracetamol suppository assay. MELC methods for paracetamol analysis and for separation of paracetamol and its impurities were previously reported. In this study, further development of MEEKC methods and a MELC method using anionic and cationic microemulsions gave excellent validation results for paracetamol content in suppositories. SDS Microemulsion instability resulted in poor reproducibility for impurity separations using gradient elution. A novel isocratic CTAB MELC method achieved reproducible separation of paracetamol and its impurities at 0.1% levels. MEEKC methods using SDS and CTAB microemulsions resolved all of the impurities however detection at 0.1% levels was not possible. These methods gave significant benefits in terms of reduced sample pre-treatment requirements. CTAB microemulsions had greater solubilising power than their SDS equivalent and were more stable due to their longer alkyl chain length.     

Enantiomeric purity determination of propranolol by capillary electrophoresis using dual cyclodextrins and a polyacrylamide-coated capillary.

The use of a chirally selective capillary electrophoresis method is reported for the enantioselective purity determination of propranolol drug substance. The method employed a combination of both charged and neutral cyclodextrin. An internally coated capillary was used to suppress electroosmotic flow and potential peak tailing. The method was capable of monitoring below 0.1% m/m of the undesired impurity. Acceptable validation data was also obtained for recovery, linearity, and for both short and long-term injection precision.     

Overview of capillary electrophoresis and capillary electrochromatography.

This paper provides an overview on the current status of capillary electrophoresis (CE) and capillary electrochromatography (CEC). The focus is largely on the current application areas of CE where routine methods are now in place. These application areas include the analysis of DNA, clinical and forensic samples, carbohydrates, inorganic anions and metal ions, pharmaceuticals, enantiomeric species and proteins and peptides. More specific areas such the determination of physical properties, microchip CE and instrumentation developments are also covered. The application, advantages and limitations of CEC are covered. Recent review articles and textbooks are frequently cited to provide readers with a source of information regarding pioneering work and theoretical treatments.     

Spherically symmetric inhomogeneous dust collapse in higher dimensional space-time and cosmic censorship hypothesis

We consider a collapsing spherically symmetric inhomogeneous dust cloud in higher dimensional space-time. We show that the central singularity of collapse can be a strong curvature or a weak curvature naked singularity depending on the initial density distribution.     

Semi-wet growth and characterization of multi-functional nano-engineered mixed metal oxides for industrial application

This review paper covers the low temperature wet growth of nano-engineered particles of ZnO-based mixed metal oxides, their growth mechanism, and characterization using X-ray diffraction, SEM, TEM and IR, UV–visible, and XPS spectral techniques. Main focus of this article is centered on low temperature semi-wet methods of synthesis that are suitable for large scale production of zinc oxide-based systems mixed with iron oxide, copper oxide, nickel oxide and cobalt oxide. These mixed metal oxides have broad industrial applications as catalyst, semiconductors, adsorbents, superconductors, electro-ceramics, and antifungal agents in addition to extensive applications in medicines. This paper discusses the low-cost and environment friendly synthesis of these mixed metal oxides, measurement of properties and applicability of these materials systems.     

Synaptic depression and short-term habituation are located in the sensory part of the mammalian startle pathway

Background  

Short-term habituation of the startle response represents an elementary form of learning in mammals. The underlying mechanism is located within the primary startle pathway, presumably at sensory synapses on giant neurons in the caudal pontine reticular nucleus (PnC). Short trains of action potentials in sensory afferent fibers induce depression of synaptic responses in PnC giant neurons, a phenomenon that has been proposed to be the cellular correlate for short-term habituation. We address here the question whether both this synaptic depression and the short-term habituation of the startle response are localized at the presynaptic terminals of sensory afferents. If this is confirmed, it would imply that these processes take place prior to multimodal signal integration, rather than occurring at postsynaptic sites on PnC giant neurons that directly drive motor neurons.     

An evaluation of the use of capillary electrophoresis to monitor trace drug residues following the manufacture of pharmaceuticals

Summary The novel use of capillary electrophoresis to the important and developing area of monitoring possible drug residues on pharmaceutical manufacturing equipment is reported. The CE method is applicable to a wide range of basic drugs with sensitivity as low as 25ng/ml (equivalent to 8×10^–8 M). This sensitivity is equivalent to that obtainable for HPLC for the drugs tested and is obtained by employing a combination of a wider bore capillary with low wavelength UV detection. Preliminary evaluation of the method performance shows acceptable precision, linearity, sensitivity and accuracy. Features of the method compared to HPLC include simplicity, ease of method transfer, reductions in analysis set-up time, and reduced costs of solvents and columns.     

An initial assessment of the use of gradient elution in microemulsion and micellar liquid chromatography

Novel microemulsion and micellar HPLC separations have been achieved using gradient elution and columns packed with reverse phase material. Initial attempts at gradient microemulsion liquid chromatography proved impossible on use of a microemulsion successfully used in capillary electrophoresis. Optimisation of the microemulsion composition allowed the generation of stable microemulsions to achieve separations in HPLC. The novel use of organic-solvent micellar chromatography in gradient elution mode was shown to give efficient separations. A range of efficient separations of pharmaceuticals and related impurities were obtained. Acidic, basic, and neutral solutes were resolved covering a wide range of water solubilities and polarities. Elution times were in the order of 4-15 minutes. Separations were briefly compared to those accomplished with a micellar HPLC system. It is proposed that gradient elution in both microemulsion and micellar HPLC can be regarded as a highly successful means of achieving resolution of complex mixtures and should be considered for routine analysis and further investigation.     

On-line solution stability determination of pharmaceuticals by capillary electrophoresis

Summary Good agreement between the impurity levels in a batch of a related impurity of ranitidine were obtained by CE and HPLC. A solution of the impurity was positioned on the CE autosampler and analysed sequentially. The extent of degradation was monitored by loss of main peak and the formation of two principal degradation products. It was found that after 9.25 hours only 2% area/area of the original impurity remained. Buffering of the sample solution to pH 7 was shown to minimise this degradation.Unattended in-situ stability testing of an solution of the impurity in water was performed by CE.