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

Rapid method for the quantitative determination of efavirenz in human plasma

A pharmacokinetic interaction study between efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor used in the treatment of HIV-1 infection, and an African traditional medicine, African potato in human subjects was undertaken. This necessitated the development and validation of a quantitative method for the analysis of EFV in plasma. A simple mobile phase consisting of 0.1 M formic acid, acetonitrile and methanol (43:52:5) was pumped at a low flow rate of 0.3 ml/min through a reverse phase Phenomenex® Luna C18 (2) (5 μm, 150 mm × 2.0 mm i.d.) column maintained at 40 °C. Diclofenac sodium was used as an internal standard (IS) and EFV and IS were monitored at 247 nm and 275 nm, respectively. A simple and rapid sample preparation involved the addition of mobile phase to 100 μl of plasma to precipitate plasma proteins followed by direct injection of 10 μl of supernatant onto the column. The procedures were validated according to international standards with good reproducibility and linear response (r = 0.9990). The intra- and inter-day accuracies were between 12.3 and 17.7% at the LLOQ and between −5.8 and 9.1% for the QC samples. The intra- and inter-day precision of EFV determinations were 5.1 or less and 7.2% RSD or less, respectively across the entire QC concentration range. Mean recovery based on high, medium and low quality control standards ranged between 92.7 and 94.1% with %RSD values better than 3%. Plasma samples were evaluated for short-term (ambient temperature for 6 h) and long-term (−10 ± 2 °C for 60 days) storage conditions and were found to be stable. The method described is cost-effective and has the necessary accuracy and precision for the rapid quantitative determination of EFV in human plasma

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

Application of reverse-flow micellar electrokinetic chromatography for the simultaneous determination of flavonols and terpene trilactones in Ginkgo biloba dosage forms

A reverse-flow micellar electrokinetic chromatographic (RF-MEKC) method was developed for the simultaneous qualitative determination of 10 components consisting of the flavonol glycosides, rutin and quercitrin, the flavonol aglycones, isorhamnetin, kaempferol and quercetin, the terpene trilactones, ginkgolides A, B, C and J and the sesquiterpene, bilobalide. This method was used to fingerprint Ginkgo biloba solid oral dosage forms and validated for the quantitation of the marker compounds, rutin and quercetin in some commercial products. In addition to the usual variables, the influence of some essential background electrolyte (BGE) components such as sodium dodecyl sulphate (SDS) and -cyclodextrin concentrations were investigated. A polyimide fused-silica square capillary column (75 μm I.D. × 360 μm O.D.) with a total length of 60.0 cm and effective length of 45.0 cm was used for the separation. The final BGE consisted of 20 mM phosphoric acid, 40 mM SDS and 12 mM -cyclodextrin (pH 2.2) using reverse polarity with a voltage of −17.5 kV. Samples were injected electrokinetically at −5 kV for 3 s for the qualitative analysis and hydrodynamically at 20 mbar for 0.6 s for the quantitative assay. The total run time was 22 min and the limits of detection were 3.13 μg/ml and 1.88 μg/ml for rutin and quercetin, respectively. Fingerprint profiles of the solid oral dosage forms and the results of the quantitative analysis indicated that there were major discrepancies in the marker content between products and illustrates the value of this method for use as a procedure to assess product quality of commercially available Ginkgo biloba products

Assessment of topical corticosteroid preparations: the human skin-blanching assay

(From the introduction) Since the introduction of topical corticosteroid formulations, their use has become widespread, being prescribed for a large variety of dermatological conditions. This widespread use has created a need for a reliable method of assessing the various dosage forms of these compounds. Clinical trials are laborious, costly and difficult to mount as well as being impractical for the screening of large numbers of drugs. Patients suffering from dermatological complaints are not ideal subjects for the testing of topical corticosteroid preparations as it is difficult to obtain standardized lesions which are necessary for the comparison of results between patients (Baker and Sattar, 1968). For these reasons a number of methods have been developed for the screening of novel corticosteroids and testing of topical corticosteroid formulations

Comparative blanching activities of some topical corticosteroid containing lotions

The blanching activities of Betnovate and Celestoderm-V lotions (betamethasone-17-valerate, 0,1%) and Diprosone lotion (betamethasone dipropionate, 0,55%) were determined by measuring their ability to cause blanching of human skin after topical application. Betnovate and Celestoderm-V lotions produced almost identical blanching profiles. Diprosone lotion displayed a statistically significant superior blanching acitivity over both Betnovate and Celestoderm-V lotions over the whole timespan of the trial

Sterols and sterolins in Hypoxis hemerocallidea (African potato)

Commercially available health supplements and herbal remedies containing sterols and sterolins, either from African potato (Hypoxis hemerocallidea) alone, or whether enriched with sterols and sterolins, are claimed to be efficacious in the treatment of a variety of ailments. Sterols and sterolins in African potato are purported to be the relevant constituents that are required for the therapeutic claims of such products. A patent describing the extraction of sterolins from African potato plant material has claimed that approximately 9 mg sterolins can be isolated from 100 g of an enriched aqueous African potato extract. Our analysis of African potato plant material and its sterol and sterolin content, when similarly prepared, shows that the measureable content of sterols and sterolins in African potato is far less than the amounts of these compounds that have been claimed to be necessary for therapeutic benefit. We conclude that therapeutic claims relating to sterol and sterolin content in African potato are unsubstantiated, in view of the extremely low content of such compounds that we have isolated from our plant material, and in products containing African potato, or extracts thereof

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

Comparative bioavailability of some locally manufactured betamethasone valerate containing preparations

The bioavailabilities of three locally manufactured proprietary betamethasone- 17-valerate containing creams and ointments were compared by measuring their abilities to cause blanching of human skin after topical application. The preparations studied were Betnovate Cream and Ointment, Celestoderm-V Cream and Ointment and Persivate Cream and Ointment. Celestoderm-V cream displayed a significantly superior blanching activity over both Betnovate and Persivate creams in' the occluded mode, whereas Persivate cream displayed a significantly superior blanching activity over both Betnovate and Celestoderm-V creams in the unoccluded mode. Persivate ointment was found to produce a significantly superior blanching activity over Betnovate and Celestoderm-V ointments in both the occluded and unoccluded modes of application

Phenylpropanolamine hydrochloride

Phenylpropanolamine hydrochloride belongs to the sympathomimetic amine class of drugs and is structurally related to ephedrine hydrochloride. Its synthesis was first reported in 1910 and the first American patent was registered in 1939. The effects of phenylpropanolamine hydrochloride are largely the result of alpha-adrenergic agonist activity resulting from both direct stimulation of adrenergic receptors and release of neuronal norepinephrine. The principal adverse effect of phenylpropanolamine hydrochloride is dose-related hypertension and ventricular arrhythmia has been described. Phenylpropanolamine hydrochloride is widely used as a decongestant and it has been used as an anorectic agent for over 40 years. A report in 1939 described its effect as an hypertensive agent when administered parenterally