Rapid, user-friendly, and inexpensive detection of azidothymidine.

Strict adherence to highly active antiretroviral therapy (HAART) is very important to improve the quality of life for HIV-positive patients to reduce new infections and determine treatment success. Azidothymidine (AZT) is an antiretroviral drug commonly used in HAART treatment. In this research, an "add, mix, and measure" assay was developed to detect AZT within minutes. Three different probes designed to release fluorophores when samples containing AZT are added were synthesized and characterized. The limit of detection to AZT in simulated urine samples was determined to be 4 µM in 5 min for one of the probes. This simple and rapid point-of-care test could potentially be used by clinicians and health care workers to monitor the presence of AZT in low resource settings.

Simple thin layer chromatography-ultraviolet spectrophotometric method for quality assessment of binary fixed-dose-combinations of lamivudine/tenofovir disoproxil fumarate and lamivudine/zidovudine in tablet formulations.

Antiretroviral fixed-dose-combination drugs are best assayed with high-performance liquid chromatography, or liquid chromatography-tandem mass spectrometry. However, most scientists in developing nations have no access to these expensive instruments. A more affordable quantitative technique is the use of ultraviolet-visible spectroscopy-where often the absorption spectra of these antiretrovirals are overlapping; thus complex derivative methodologies are required for quantification. A simple, rapid, and accurate thin layer chromatography-ultraviolet spectrophotometric method for the quantification of binary mixtures of lamivudine, zidovudine, and tenofovir-disoproxil-fumarate in tablet formulations was developed. Lamivudine/tenofovir-disoproxil-fumarate and lamivudine/zidovudine were extracted and separated on glass thin-layer chromatography plates. Drugs were identified in ultraviolet light at 254 nm and quantified in acidic medium using ultraviolet spectrophotometry. The retardation factors were 0.43, 0.79, and 0.81 for lamivudine, tenofovir-disoproxil-fumarate, and zidovudine, respectively, with corresponding absorption maxima at 270, 260, and 265 nm. Linearity ranged from 1 to 40 µg/mL for all drugs (R = 0.9998-0.9999), while recovery studies were 95.10-102.11% and amount in formulations ranged from 97.99 ± 0.63 to 101.47 ± 2.39%. The paired t-test (n = 5) indicated no significant difference between the proposed and high-performance liquid chromatography methods, hence comparable and can be used as an alternative method in routine quality determination of antiretroviral medicines.

Risk of false conformity decisions of multicomponent items controlled by correlated measurement results due to the sharing of analytical steps.

The assessment of the conformity of some items, such as medicines, food products or drinking waters, with limits set for several of their components, involves the determination of these components using multi-analyte measurement procedures. Since these determinations involve the sharing of relevant analytical steps, such as the sample preparation and analytical instrument run, the measurement results of the various components become correlated (i.e. 'between components metrologically correlated'). The closeness of the values of the components to the respective tolerance limits, the measurements uncertainty and the correlation of the measurements results affects the risk of false conformity decisions of the analysed item. This correlation can either increase or decrease the risk of false conformity decision and is relevant to decide if the item should be considered conform or not conform with the regulation. This work presents a methodology to estimate the 'between components metrological correlation' of results of the analysis of an item subsequently used to assess the impact of this correlation on the risk of false conformity decisions. The methodology was successfully applied to the assessment of the conformity of pharmaceutical tablets against tolerance limits for lamivudine (3TC) and zidovudine (AZT) determined from the analysis of the same analytical portion in the same HPLC-UV/Vis run. The correlation of measurement results was determined from Monte Carlo simulations of shared analytical operation (linear correlation coefficient of 0.53) being their impact on conformity decisions relevant. For instance, for measurement results of 3TC and AZT equal to the upper limit and lower limit, respectively, the risk of a wrong acceptance of the medicines is 84% while if it is assumed that measurement results are independent this risk would be wrongly considered as 75%. The Excel® spreadsheet used for this assessment is made available as supplementary material.

Evaluación de desempeño del método de ensayo de disolución para tabletas de zidovudina 300 mg producidas en Cuba / Performance assessment of dissolution assay method of 300 mg of Zidovudine tablets produced in Cuba

Se validó un método por cromatografía líquida de alta resolución para evaluar la disolución de las tabletas de zidovudina 300 mg producidas en Cuba, con detección ultravioleta a 265 nm. Se evaluaron los parámetros de especificidad, linealidad, precisión e influencia de la filtración. En el estudio de la influencia de la filtración se demostró que a través del filtro de línea, no se absorbe el principio activo, ni se aportan interferencias al filtrado, por lo que se recomienda su empleo. Se demostró la especificidad del método al no observarse interferencias de los excipientes de la formulación, en la determinación del principio activo. La curva de linealidad se realizó en el intervalo de concentraciones estudiadas con un coeficiente de correlación igual a 0,999. El método resultó preciso ya que los valores se encontraron dentro de los límites establecidos. Se realizó además la comparación estadística de los perfiles de disolución de las tabletas producidas en Cuba contra el Retrovir® (medicamento líder), lo cual demostró que existe similitud entre el perfil de liberación de las formulaciones

A high-performance liquid chromatography method was validated to assess the dissolution of 300 mg Zidovudine tablets manufactured in Cuba with 265 nm ultraviolet (UV) detection. Filtration specificity, linearity, accuracy parameters were assessed. In influence filtration study it was shown that through the line-filter the active principle it isn't absorbed and without filtrate interferences thus it is recommended its use. It was possible to demonstrate the method specificity due to no interferences of the formula excipients in active principle assessment. Linearity curve was drawed in the interval of study concentrations with a correlation coefficient similar to 0.999. The method was precise since the values were within the established limits. Also, we made a statistical comparison of dissolution profiles of tablets manufactured in Cuba versus Retrovir® (leading drug) demonstrating that there is a similarity between the formulas release profile

Novel conducting polymer functionalized with metal-cyclam complex and its sensor application: development of azidothymidine drug sensor.

Functionalization of polyanthranilic acid (PAA) a self-doped conducting polymer with Co(II) metal complex has been reported and is used in the development of azidothymidine drug sensor. For the first time synthesis of a new type of polymer complex of Co(II)-cyclam macrocyclic ligand (1,4,8,11-tetraazacyclotetradecane) with carboxylated polymer (as a second ligand) has been successfully accomplished and discussed in the present paper. The interaction of Co(II)-cyclam complex with polyanthranilic acid has been studied in solution phase using UV-vis spectra. Further, the formation and growth study of mixed ligand complex is carried out using electrochemical quartz crystal microbalance. The characterization of solid mixed ligand complex Co(II)-cyclam-polyanthranilic acid (Co(II)-Cy-PAA) has been carried out for its structural, thermal and electrochemical properties using various techniques viz. FT-IR, SEM, ESR, DSC, impedance and electrochemical techniques. Electrochemical study shows the potential of mixed ligand complex towards catalytic and sensor applications. The mixed ligand complex for the first time is used in the development of "azidothymidine" anti-HIV drug sensor. The analysis of azidothymidine is known over hanging drop mercury electrode using electroreduction technique, however, for the first time its analysis is reported over graphite paste electrode modified with newly synthesized mixed ligand complex. Azidothymidine is quantified in wide range of concentration with 1 microM detection limit over modified graphite paste electrode, which shows potential to develop users friendly (non-toxic and simple) gadgets and low cost screen printed electrodes.

Quantitative determination and sampling of lamivudine and zidovudine residues for cleaning validation in a production area.

Lamivudine (3TC) and zidovudine (AZT) are systemic antiviral substances extensively used in human immunodeficiency virus (HIV) infected patients. Nowadays, 3TC, AZT, and several other pharmacologically potent pharmaceuticals are manufactured in the same production area. To assure quality of drug products and patient safety, properly validated cleaning methodology is necessary. A carefully designed cleaning validation and its evaluation can ensure that residues of 3TC and AZT will not carry over and cross contaminate the subsequent product. The aim of this study was to validate a simple analytical method for verification of residual 3TC and AZT in equipment used in the production area and to confirm the efficiency of the cleaning procedure. The liquid chromatography method was validated using a Nova-Pak C18 column (3.9 x 150 mm, 4 microm particle size) and methanol-water (20 + 80, v/v) as the mobile phase at a flow rate of 1.0 mL/min. Ultraviolet detection was made at 266 nm. The calibration curve was linear over a concentration range of 2.0-22.0 microg/mL with a correlation coefficient of 0.9998. The detection and quantitation limits were 0.36 and 1.21 microg/mL, respectively. The intra-day and interday precision expressed as relative standard deviation were below 2.0%. The mean recovery of the method was 99.19%. The mean extraction recovery from manufacturing equipment was 83.5%.