Application of a rapid and selective method for the simultaneous determination of carebastine and pseudoephedrine in human plasma by liquid chromatography-electrospray mass spectrometry for bioequivalence study in Korean subjects.

We describe a simple, rapid and sensitive high-performance liquid chromatography-electrospray ionization tandem mass spectrometric method that was developed for the simultaneous determination of carebastine and pseudoephedrine in human plasma using cisapride as an internal standard. Acquisition was performed in multiple-reaction monitoring mode by monitoring the transitions: m/z 500.43 > 167.09 for carebastine and m/z 166.04 > 147.88 for pseudoephedrine. The devised method involves a simple single-step liquid-liquid extraction with ethyl acetate. Chromatographic separation was performed on a C(18) reversed-phase chromatographic column at 0.2 mL/min by isocratic elution with 10 mM ammonium formate buffer-acetonitrile (30:70, v/v; adjusted to pH 3.3 with formic acid). The devised method was validated over 0.5-100 ng/mL of carebastine and 5-1000 ng/mL of pseudoephedrine with acceptable accuracy and precision, and was successfully applied to a bioequivalence study involving a single oral dose (10 mg of ebastine plus 120 mg of pseudoephedrine complex) to healthy Korean volunteers.

Determination of cisapride, its oxidation product, propyl and butyl parabens in pharmaceutical dosage form by reversed-phase liquid chromatography.

A simple, rapid and reproducible high-performance liquid chromatography (HPLC) assay for cisapride, its oxidation product (OP), propyl and butyl parabens in a pharmaceutical formulation is described. Chromatography was performed at room temperature by pumping acetonitrile-20 mM phosphate buffer pH 7 (50:50, v/v) at 1.5 ml min(-1) through C8 reversed-phase column. Cisapride, OP, propyl and butyl parabens were detected at 276 nm and were eluted at 9.7, 3.1, 5.1 and 7.1 min, respectively. Calibration plots were linear (r>0.999) for all compounds from 0.5 to 200 microg ml(-1) for cisapride and OP and 0.1-200 microg ml(-1) for propyl and butyl parabens. Detection limits for cisapride, OP, propyl and butyl parabens were 40, 46, 48 and 54 ng ml(-1), respectively. Forced degradation investigations showed that cisapride does not undergo degradation under heat, acidic and basic conditions but it was susceptible to oxidation. The proposed method was successfully applied to the assay of cisapride in the presence of preservatives and OP in a commercial suspension.

High performance liquid chromatographic determination, pharmacokinetic and comparative bioavailability studies of cisapride.

A sensitive and specific reversed phase HPLC method was developed to quantitate plasma levels of cisapride in order to conduct comparative bioavailability studies. The drug and internal standard was extracted from plasma with heptane-isoamyl alcohol (95:5 v/v) and back extracted with sulfuric acid. The acidic layer was then re-extracted with the same extracting solvent. The separated organic layer was evaporated to dryness under nitrogen and the residue reconstituted with acetonitrile. Analysis was performed on a C-8 Sil-X-10 HPLC column, with a mobile phase of acetonitrile, water, and triethylamine (75:25:0.01) and UV detection at 215 nm. The standard curve covering the concentration range 5-160 ng/ml was linear (r(2)=0.9992), relative errors were within +/-10% and the CV% ranged from 1.34 to 11.82. The in vivo study was carried out in 12 healthy volunteers according to a single dose, two-sequence, cross over randomized design. The bioavailability was compared using the total area under the plasma level versus time curve (AUC(0-34,) AUC(0- infinity )), peak plasma concentration (C(max)) and time to C(max) (T(max)). No statistically significant difference was found between the AUC(0- infinity ) or C(max) values of the test (cisapride) and reference (Propulsid). It was, therefore, concluded that the generic cisapride was bioequivalent with the innovator formulation.

Spectrophotometric determination of some chemotherapeutic agents using acetyl acetone.

Acetyl acetone is introduced as a new coupling agent for the spectrophotometric determination of some chemotherapeutic agents, such as metoclopramide, dapsone, p-aminobenzoic acid, and cisapride in both pure and dosage forms. The method is based on the diazo-coupling reaction of these chemotherapeutic agents with a new coupling agent, acetyl acetone, in an alkaline medium. The optimum reaction conditions and other analytical parameters are evaluated. The influence of the substrates commonly employed as excipients with these chemotherapeutic agents has been studied. The method is simple, rapid, and sensitive. The results obtained compare favorably with those obtained with other reference methods.

Determination of cisapride in pharmaceutical preparations using derivative spectrophotometry.

Derivative spectrophotometric and high performance liquid chromatographic methods (HPLC) were described for the determination of cisapride in pharmaceutical preparations. Spectrophotometrically, cisapride was determined by measuring the 1D-values at 264, 300 nm and 2D-values at 276, 290 and 276-290 nm. Beer's Law was obeyed in the range 2-12 microg ml(-1). The HPLC method depends upon using micropack-Si-10 column at ambient temperature with a mobile phase consisting of methanol-concentrated ammonia (99.25:0.75) at a flow rate of 1 ml min(-1). Quantitation was achieved by UV detection at 272 nm using quinine as internal standard. Calibration curve was linear over the concentration range 2-10 microg ml(-1). Both derivative spectrophotometry and HPLC methods showed good linearity, precision and reproducibility. No interference was found from tablet or suspension matrices at the selected derivative wavelengths and chromatographic conditions. The proposed methods were successfully applied to the assay of commercial tablets and suspension. The procedures were rapid, simple and suitable for quality control applications.

Stability of alprazolam, chloroquine phosphate, cisapride, enalapril maleate, and hydralazine hydrochloride in extemporaneously compounded oral liquids.

The stability of five drugs commonly prescribed for use in oral liquid dosage forms but not commercially available as such was studied. Alprazolam 1 mg/mL, chloroquine phosphate 15 mg/mL, cisapride 1 mg/mL, enalapril maleate 1 mg/mL, and hydralazine hydrochloride 4 mg/mL were each prepared in a 1:1 mixture of Ora-Sweet and Ora-Plus (Paddock Laboratories), a 1:1 mixture of Ora-Sweet SF and Ora-Plus, and cherry syrup and placed in 120-mL amber clear polyethylene terephthalate bottles. Three bottles of each liquid were stored at 5 degrees C and three at 25 degrees C, all in the dark. Samples were taken initially and at various times up to 60 days for analysis by high-performance liquid chromatography and assessment of appearance and odor; pH was measured. A mean of at least 91% of the initial drug concentration was retained for 60 days in the alprazolam, chloroquine phosphate, cisapride, and enalapril maleate liquids. The hydralazine hydrochloride liquids retained more than 90% of the initial concentration for only one day at 5 degrees C when prepared with Ora-Sweet-Ora-Plus and two days when prepared with Ora-Sweet SF-Ora-Plus and for less than a day in these preparations at 25 degrees C and in cherry syrup at 5 and 25 degrees C. No substantial changes in the appearance, odor, or pH of any liquid were observed. Alprazolam 1 mg/mL, chloroquine phosphate 15 mg/mL, cisapride 1 mg/mL, and enalapril maleate 1 mg/mL were stable in three extemporaneously compounded oral liquids for 60 days at 5 and 25 degrees C; hydralazine hydrochloride 4 mg/mL was stable at 5 degrees C for one day in Ora-Sweet-Ora Plus and for two days in Ora-Sweet SF-Ora-Plus.