Venlafaxine Determination in Pharmaceutical Formulation and Serum by Ion-Selective Electrodes.

BACKGROUND: The application of an ion selective technique for the determination of analyte concentrations is considered one of the most economical techniques for quality control purposes. OBJECTIVE: To elaborate and investigate the construction and general performance characteristics of potentiometric PVC membrane sensors for venlafaxine cation (Ven+). METHOD: The sensors are based on the use of the ion association complexes of the venlafaxine cation with phosphotungstate (PT) and silicotungstate (ST) counter anions as ion exchange sites in the plasticized PVC matrix. They are characterized by potentiometric and conductimetric measurements, performed under various conditions. RESULTS: The electrodes showed a fast (response time around 15 s), stable (life span 45 days) and linear (r2 0.995) response for venlafaxine over the concentration range of 5x10-5 - 1x10-2 M venlafaxine hydrochloride. The solubility product of the ion pair and the formation of the precipitation reaction leading to the ion pair, were determined conductimetrically. The electrodes were found to be very selective, precise (RSD < 1%) and applicable to the potentiometric determination of venlafaxine hydrochloride in pure solutions or in pharmaceutical preparation and in biological fluid (serum), without any interference. Validation of the method shows the suitability of the proposed electrodes for use in the quality assessment of venlafaxine hydrochloride. CONCLUSION: Using only a pH meter in combination with the selective electrodes, drug substance or drug product could be determined accurately in a few seconds. In addition, the in-house made electrodes were tested to monitor venlafaxine in serum. Acceptable results were achieved using the standard addition technique.

Development and validation of a liquid chromatographic method for the analysis of squaric acid dibutyl ester and its impurities.

A simple, fast and selective stability indicating liquid chromatographic method has been described for the simultaneous determination of squaric acid dibutyl ester and its impurities. The chromatographic separation was achieved on a C2 column (250mm×4.6mm i.d., 5µm) using a mobile phase consisting of 0.15% phosphoric acid - acetonitrile - methanol (30:60:10, v/v/v). Isocratic elution was performed at a flow rate of 1.0mLmin-1. The analytes were detected by UV at 252nm. The method was validated according to the ICH guidelines and satisfactory results were obtained. The specificity of the developed method was tested using forced degradation solutions of the drug substance. Characterization of squaric acid dibutyl ester and its forced degradation products was achieved by coupling mass spectrometry (MS) to the liquid chromatographic (LC) system. The method was successfully applied for quality control purposes including assay and determination of related compounds as required by regulatory guidelines to ensure its safety and efficacy since no monograph is available in official compendia.

Stability of Drugs Used in Helicopter Air Medical Emergency Services: An Exploratory Study.

OBJECTIVE: Transportation by air exposes drugs used in emergency medical services to vibrations. The aim of the study was to determine whether or not vibrations caused by a helicopter induce the degradation of 5 drugs used in this setting. METHODS: A longitudinal study in an operating medical helicopter along with a worst case was conducted. The studied drugs were 3 drugs labeled for refrigeration (cisatracurium, lorazepam, and succinylcholine) and 2 albumin solutions (human albumin 4% and 20%). These drugs were stored for 4 months according to the following conditions: inside a helicopter, worst case with exposure to extreme vibrations, at room temperature, and according to manufacturers' recommendations. Samples were analyzed with validated high-performance liquid chromatography assay methods. A drug was considered stable if the remaining drug content was above 90% of the label claim. Except for the albumin solutions, visual inspection was used to determine instability by the formation of aggregates. RESULTS: Only the samples stored at room temperature became unstable after 4 months. No difference in extreme foaming was observed in the albumin solutions. CONCLUSIONS: These data suggest that the effect of degradation of drugs caused by vibrations is negligible. Temperature was observed as the main cause of drug degradation.

Simultaneous determination of chlordiazepoxide and selected antidepressants using CZE.

A simple CE method was developed and validated for the simultaneous determination of chlordiazepoxide (CHL), amitriptyline, and nortriptyline (mixture I) or the determination of CHL and imipramine (mixture II) using the same BGE. Sertraline and amitriptyline were used as internal standards for the first and second mixtures, respectively. The method allows amitriptyline to be completely separated from its impurity and main metabolite nortriptyline, which can be quantified from 0.2 µg/mL. The separation was achieved using 20 mM potassium phosphate buffer pH 5 containing 12 mM ß-cyclodextrin and 1 mM carboxymethyl-ß-cyclodextrin. UV detection was performed at 200 nm and a voltage of 15 kV was applied on an uncoated fused-silica capillary at 25°C. These experimental conditions allowed separation of the compounds to be obtained in 7 min. Calibration graphs proved the linearity up to 40 µg/mL for CHL, up to 100 µg/mL for amitriptyline and imipramine, and up to 5 µg/mL for nortriptyline. The accuracy and precision of the method have been determined by analyzing synthetic mixtures and pharmaceutical formulations. The analytical results were quite good in all cases indicating that the method was linear, sensitive, precise, accurate, and selective for both mixtures.