Rapid and sensitive simultaneous separation and electrochemical detection of tetracaine hydrochloride and oxymetazoline hydrochloride in pharmaceutical formulations via core-shell reversed-phase liquid chromatography.

Tetracaine hydrochloride (TCH) is a nasal anesthetic and oxymetazoline hydrochloride (OZH) is a nasal decongestant. A moderate to acute overdosage of OZH and TCH can lead to mydriasis, nausea, cyanosis, tachycardia, dyspnoea, cardiovascular failure, disorientation, seizures, and even death. Liquid chromatography (LC) has been mainly utilized for the individual determination of either TCH or OZH; however, there is a need for rapid and efficient methods for simultaneous analysis in pharmaceutical formulations and aqueous samples. This study highlights the use of the fast and efficient separation capabilities of core-shell silica particles in liquid chromatography (LC) for the simultaneous determination of TCH and OZH using UV detection and the enhanced selectivity afforded by electrochemical detection at a boron-doped diamond (BDD) electrode. Rapid reversed-phase (RP) separation and detection of OZH and TCH in nasal spray and eye drops was achieved within 45 s using a poroshell 120 EC-C18 column, by adjusting the ratio of organic solvent, mobile phase pH, detection potential and mobile phase flow rate. Sensitivity was compared using ultraviolet (UV) detection at 280 nm, and ECD at + 1.3 V with detection limits of 40 and 70 nM for TCH and OZH, respectively. The developed rapid method was utilized successfully in the analysis of pharmaceutical formulations, where the estimated levels of TCH and OZH in these formulations are in agreement with the specified values outlined by the manufacturers.

Utilization of Localized Surface Plasmon Resonance of Silver Nanoparticles for the Spectrofluorimetric Estimation of Oxymetazoline in Dosage Forms: Application to Aqueous Humor.

A simple, novel, cost-effective and highly sensitive spectrofluorimetric method was developed for estimation of the nasal decongestant oxymetazoline (OMZ) whether per se or in its pharmaceutical preparations using colloidal silver nanoparticles (AgNPs). The method is based on the high catalytic potential activity of AgNPs on the fluorescence intensity of OMZ leading to 12-fold increase in its fluorescence intensity. The response was linear over the range of 20.0 to 700.0 ng/mL with lower detection limit of 5.0 ng/mL and limit of quantification of 14.0 ng/mL. The proposed method was applied to the assay of commercial nasal drops, nasal spray and synthetic aqueous humor. Interference likely to be encountered from co-administered drugs was studied. The developed method was optimized and validated as per International Council of Harmonization (ICH). An explanation for the drug-AgNPs interaction was proposed.

Simultaneous Determination of Cromolyn Sodium Combined Dosage Forms Using Isocratic HPLC Method.

A simple and selective reversed-phase high-performance liquid chromatography method was developed for the estimation of cromolyn sodium (CRM) with either oxymetazoline hydrochloride (OMZ) or xylometazoline hydrochloride (XMZ) in their binary mixtures. The method is based on the simultaneous separation of each drug in a reversed-phase Waters symmetry® C18 column (250 mm × 4.6 mm intradermally, 5-µm particle size) at 25°C. Elution was performed with a mobile phase consisting of methanol : 0.1 M phosphate buffer (60:40, v/v, pH 4.0). Quantitation was achieved with ultraviolet detection at 220 nm. The method could determine the three drugs, with linearity, in the range of 2.0-100.0 µg/mL for CRM and 0.8-8.0 µg/mL for OMZ and for XMZ. Aspirin was used as internal standard. Optimization of the separation in terms of mobile phase composition is critical to the method development, which is discussed in detail. The suggested procedure was successfully applied to the analysis of the studied drugs in their nasal preparations. Statistical evaluation of the data obtained by the proposed and comparison methods revealed good accuracy of the proposed method.

Novel spectroscopic methods for determination of Cromolyn sodium and Oxymetazoline hydrochloride in binary mixture.

New accurate, sensitive and selective spectrophotometric and spectrofluorimetric methods were developed and subsequently validated for determination of Cromolyn sodium (CS) and Oxymetazoline HCl (OXY) in binary mixture. These methods include 'H-point standard addition method (HPSAM) and area under the curve (AUC)' spectrophotometric method and first derivative synchronous fluorescence spectroscopic (FDSFS) method. For spectrophotometric methods, absorbances were recorded at 241.5nm and 274.9nm for HPSAM and the wavelength was selected in ranges 232.0-254.0nm and 216.0-229.0nm for AUC method, where the concentration was obtained by applying Cramer's rule. For FDSFS method, the first-derivative synchronous fluorescence signal was measured at 290.0nm, using Δλ=145.0nm. The suggested methods were validated according to International Conference of Harmonization (ICH) guidelines and the results revealed that they were precise and reproducible. All the obtained results were statistically compared with those of the reported method and there was no significant difference.

Flow-injection chemiluminescence method for the determination of naphazoline hydrochloride and oxymetazoline hydrochloride.

A sensitive and simple flow-injection chemiluminescence (FI-CL) method, which was based on the CL intensity generated from the redoxreaction of potassium permanganate (KMnO4)-formaldehyde in vitriol (H2SO4) medium, has been developed, validated and applied for the determination of naphazoline hydrochloride and oxymetazoline hydrochloride. Besides oxidants and sensitizers, the effect of the concentration of H(2)SO(4), KMnO4 and formaldehyde was investigated. Under the optimum conditions, the linear range was 1.0 x 10(-2)-7.0 mg/L for naphazoline hydrochloride and 5.0 x 10(-2)-10.0 mg/L for oxymetazoline hydrochloride. During seven repeated inter-day and intra-day precision tests of 0.1, 1.0 and 10.0 mg/L samples, the relative standard deviations all corresponded to reference values. The detection limit was 8.69 x 10(-3) mg/L for naphazoline hydrochloride and 3.47 x 10(-2) mg/L for oxymetazoline hydrochloride (signal-to-noise ratio < or = 3). This method has been successfully implemented for the determination of naphazoline hydrochloride and oxymetazoline hydrochloride in pharmaceuticals.

Simultaneous determination of triamcinolone acetonide and oxymetazoline hydrochloride in nasal spray formulations by HPLC.

A high-performance liquid chromatography (HPLC) method with UV detection at 232 nm was developed and validated for the simultaneous determination of triamcinolone acetonide (TAA) and oxymetazoline hydrochloride (OXY) in nasal spray formulations. The chromatographic system consisted of a micro Bondapak CN column (150 mm x 3.9 mm), 5 microm particle size with a mobile phase composition of acetonitrile:ammonium acetate (pH 5.0, 20mM) (10:90, v/v) at a flow rate of 1.0 mL/min. Calibration curves were linear for both TAA and OXY in the concentration range of 2.5-25.0 microg/mL. The limit of detection and quantitation were 0.29 and 0.88 microg/mL for OXY and 0.24 and 0.73 microg/mL for TAA. The described method was further applied to the analysis and stability studies of two nasal spray formulations I and II prepared from TAA and OXY commercial nasal spray products. The stability of OXY and TAA in the commercial products and the nasal formulations I and II were analyzed after 30 days at room temperature and 30 days at 40 degrees C/60% relative humidity. The results of the stability study showed that OXY and TAA in the commercial nasal spray products and the nasal formulations I and II were stable at 20-25 degrees C (room temperature) but TAA was unstable at 40 degrees C/60% relative humidity. TAA exhibited more than 10% loss at 14 days in both the nasal formulations and in the commercial products. OXY showed increased degradation at 40 degrees C/60% relative humidity but <10%.

The stability of oxymetazoline hydrochloride in aqueous solution.

The kinetics of the hydrolysis reaction of oxymetazoline hydrochloride in aqueous solution at three temperatures (343 K, 353 K, 363 K), over the pH-range 0.5-12.5 and ionic strength 0.5 has been investigated. The changes of concentration of oxymetazoline hydrochloride were followed by the HPLC method with UV detection. In the pH range from 0.45 to 12.50, the hydrolysis of oxymetazoline consists of hydrolysis of oxymetazoline molecules catalyzed by hydrogen ions, spontaneous hydrolysis of the dissociated and undissociated oxymetazoline molecules. A minimal rate of the hydrolysis oxymetazoline was observed to occur in the pH range from 2.0 to 5.0. Thermodynamic parameters of the reaction: energy, entropy and enthalpy of activation and the frequency factor for the specific rate constants were determined.

Determination of oxymetazoline hydrochloride and decomposition products by high-performance liquid chromatography.

An HPLC method for the separation of the oxymetazoline hydrochloride and the products of its decomposition was developed and validated. The determination was performed with a LiChrospher RP-18 column, mobile phase of methanol-H2O-triethylamine-sodium acetate (1 mol l(-1))-acetic acid (1.06 kg l(-1)) (130:60:6:2:1). UV detector set at 280 nm and antazoline methanesulfonate as an internal standard.