Sensitive high-performance liquid chromatographic determination of cyclizine and its demethylated metabolite, norcyclizine, in biological fluids using coulometric detection

An accurate, sensitive, selective and reproducible high-performance liquid chromatographic method with coulometric detection for the determination of cyclizine and its inactive demethylated metabolite, norcyclizine, in biological fluids has been developed. The drugs were separated using a custom packed reversed-phase C18 analytical column and phosphate buffer (0.05 M, pH 3)-acetonitrile (7:3) as mobile phase. The dual electrode coulometric detector was operated in the "oxidative-screen" mode with the upstream electrode (detector 1) set at 0.55 V and the downstream electrode (detector 2) set at 0.90 V. Serum and urine samples were prepared for analysis by solid-phase extraction, followed by a simple phase-separation step. The limit of quantitation was 1 ng/ml for both cyclizine and norcyclizine in serum and urine

A capillary zone electrophoresis (CZE) method for the determination of cyclizine hydrochloride in tablets and suppositories

Current compendial methods of assay for the analysis of cyclizine tablets involve the use of UV spectrophotometry. Since this is a non-selective technique its application to more complex dosage forms, such as suppositories, is unlikely to be appropriate. There is therefore a need for the development of a highly specific quantitative analytical method, such as high performance liquid chromatography (HPLC) or capillary electrophoresis (CE). The latter technique was chosen in view of some specific advantages over HPLC, such as the use of relatively non-toxic aqueous buffers, as opposed to organic solvents, which obviates the use of expensive HPLC grade solvents making CE more cost effective. Cyclizine was analyzed in 50 mM phosphate buffer (pH 2.3) and run at an applied voltage 25 kV. Detection sensitivity was enhanced by using a wavelength of 200 nm and samples were loaded hydrodynamically onto an uncoated fused-silica capillary (60 cm×50 mm i.d.). Chlorcyclizine was used as the internal standard and resolution of both compounds was achieved in less than 7 min. Stress testing was undertaken in order to investigate the appearance of breakdown products. The method has the requisite accuracy, selectivity, sensitivity and precision to assay cyclizine in tablets and suppositories. Degradation products resulting from the stress studies did not interfere with the detection of cyclizine and the assay is thus stability-indicating

Sex differences in the effects of visual contact and eye contact in negotiations

"Previous research has proposed that the ability to see others would benefit negotiations. We argue that this view is too narrow and that the impact of visual contact on negotiated agreements depends on the meaning individuals ascribe to either its presence or absence. Based on previous research showing that females are more likely to understand others in the presence of visual contact while males understand others better in the absence of visual contact, we explore how visual contact, eye contact, and sex affect the quality of negotiated agreements in a meta-analysis (Study 1) and a laboratory experiment (Study 2). The two studies combined show that because direct communication via the face facilitates a shared understanding for two unacquainted females, their agreements are of higher quality when they have visual contact compared to when they do not (Study 1), and if they have visual contact, their agreements are better when they have eye contact than when they do not (Study 2). Because communication via the face increases discomfort between two unacquainted males, their agreements are of higher quality when they do not have visual contact (Study 1), and if they do have visual contact, their agreements are better when they have no eye contact than when they do (Study 2)." [author's abstract

A review of heterogeneous interpretations of emotional reactivity

‘Emotional reactivity’ (ER) is an important construct in the analysis of individual temperamental differences, and has accounted for significant variance in studies with respect to its definition. Between 1920 and 2015, the meaning of ER has varied from physiology of emotional reactions, to stress, depression, and as a subtype of empathy. This paper highlights the confusion in the literature about the meaning of ER and raises questions about the current use of the term ER as a valid construct. It clarifies heterogeneity within ER through the creation of a framework to explain different subtypes of ER and suggests new labels designed to help researchers specify the constructs underpinning the term ER.peer-reviewe

Generic substitution: the use of medicinal products containing different salts and implications for safety and efficacy

In their quest to gain early entry of new generic products into the market prior to patent expiration, one of the strategies pursued by generic drug product manufacturers is to incorporate different salts of an approved active pharmaceutical ingredient (API) in a brand company's marketed dosage form and subject such dosage forms to bioequivalence assessment. These initiatives present challenges to regulatory authorities where the decision to approve bioequivalent products containing such pharmaceutical alternatives must be considered in the light of safety and efficacy, and more particularly, with respect to their substitutability. This article describes the various issues and contentions associated with the concept of pharmaceutical alternatives, specifically with respect to the uses of different salts and the implications for safety, efficacy and generic substitution

Analysis of macrolide antibiotics

The following macrolide antibiotics have been covered in this review: erythromycin and its related substances, azithromycin, clarithromycin, dirithromycin, roxithromycin, flurithromycin, josamycin, rokitamycin, kitasamycin, mycinamycin, mirosamycin, oleandomycin, rosaramicin, spiramycin and tylosin. The application of various thin-layer chromatography, paper chromatography, gas chromatography, high-performance liquid chromatography and capillary zone electrophoresis procedures for their analysis are described. These techniques have been applied to the separation and quantitative analysis of the macrolides in fermentation media, purity assessment of raw materials, assay of pharmaceutical dosage forms and the measurement of clinically useful macrolide antibiotics in biological samples such as blood, plasma, serum, urine and tissues. Data relating to the chromatographic behaviour of some macrolide antibiotics as well as the various detection methods used, such as bioautography, UV spectrophotometry, fluorometry, electrochemical detection, chemiluminescence and mass spectrometry techniques are also included

A stability-indicating high performance liquid chromatographic assay for the determination of orlistat in capsules

A stability-indicating HPLC method was developed and validated for the quantitative determination of orlistat in capsule dosage forms. An isocratic separation was achieved using a Perfectsil® target ODS-3, 250 mm × 4.6 mm i.d., 5 µm particle size column with a flow rate of 0.7 ml/min and using a UV detector to monitor the eluate at 210 nm. The mobile phase consisted of methanol:acetonitrile:trifluoroacetic acid (82.5:17.5:0.01, v/v/v). The drug was subjected oxidation, hydrolysis, photolysis and heat to apply stress conditions. Complete separation was achieved for the parent compound and all degradation products in an overall analytical run time of approximately 15 min with the parent compound orlistat eluting at approximately 9 min. The method was linear over the concentration range of 0.02–0.75 mg/ml (r = 0.9998) with a limit of detection and quantitation 0.006 and 0.02 mg/ml, respectively. The method has the requisite accuracy, selectivity, sensitivity and precision to assay orlistat in capsules. Degradation products resulting from the stress studies did not interfere with the detection of orlistat and the assay is thus stability-indicating

Analytical description of mixed ohmic and space-charge-limited conduction in single-carrier devices

While space-charge-limited current measurements are often used to characterize charge-transport in relatively intrinsic, low-mobility semiconductors, it is currently difficult to characterize lightly or heavily doped semiconductors with this method. By combining the theories describing ohmic and space-charge-limited conduction, we derive a general analytical approach to extract the charge-carrier density, the conduction-band edge and the drift components of the current density-voltage curves of a single-carrier device when the semiconductor is either undoped, lightly doped or heavily doped. The presented model covers the entire voltage range, i.e., both the low-voltage regime and the Mott-Gurney regime. We demonstrate that there is an upper limit to how doped a device must be before the current density-voltage curves are significantly affected, and we show that the background charge-carrier density must be considered to accurately model the drift component in the low-voltage regime, regardless of whether the device is doped or not. We expect that the final analytical expressions presented herein to be directly useful to experimentalists studying charge transport in novel materials and devices