Determination Of Tenofovir Disoproxil Fumarate Research Articles

Design and application of supramolecular based solid-contact ion-selective electrode for selective green determination of tenofovir disoproxil fumarate

This work describes the fabrication of solid-contact potentiometric sensor to determine the antiviral drug; tenofovir disoproxil fumarate. Screen-printed carbon electrodes have been selected as being a disposable substrate material. Ion sensing membrane is based on Polyvinyl chloride (PVC) polymer that was impregnated with calix [6] arene as being an ionophore for facilitating transferring the drug of interest from the sample phase into the membrane phase through decreasing Gibbs free energy of transfer. We applied a graphene nanocomposite interlayer between the carbon substrate and the polymeric membrane for overcoming potential drift, which is commonly encountered in solid-contact potentiometric sensors. As a result, the graphene nanocomposite layer enhanced the sensor performance and stabilized the potential signal as compared to the control sensor. The sensor performance characteristics were studied according to International Union of Pure and Applied Chemistry (IUPAC) recommendations, and linear range has been 0.01 M - 10 μM with limit of detection (LOD) 7.3 μM. We utilized the sensor for inline determination of the release of tenofovir disoproxil fumarate from its tablet pharmaceutical formulation without any separation or sample pre-treatment steps. In an attempt to be eco-friendly through evaluating the suggested method regarding its greenness, the method has been found to be excellent green according to the eco scale method.

Fast and Ultrasensitive Electrochemical Detection for Antiviral Drug Tenofovir Disoproxil Fumarate in Biological Matrices.

Tenofovir disoproxil fumarate (TDF) is an antiretroviral medication with significant curative effects, so its quantitative detection is important for human health. At present, there are few studies on the detection of TDF by electrochemical sensors. This work can be a supplement to the electrochemical detection of TDF. Moreover, bare electrodes are susceptible to pollution, and have high overvoltage and low sensitivity, so it is crucial to find a suitable electrode material. In this work, zirconium oxide (ZrO2) that has a certain selectivity to phosphoric acid groups was synthesized by a hydrothermal method with zirconyl chloride octahydrate as the precursor. A composite modified glassy carbon electrode for zirconium oxide-chitosan-multiwalled carbon nanotubes (ZrO2-CS-MWCNTs/GCE) was used for the first time to detect the TDF, and achieved rapid, sensitive detection of TDF with a detection limit of sub-micron content. The ZrO2-CS-MWCNTs composite was created using sonication of a mixture of ZrO2 and CS-MWCNTs solution. The composite was characterized using scanning electron microscopy (SEM) and cyclic voltammetry (CV). Electrochemical analysis was performed using differential pulse voltammetry (DPV). Compared with single-material electrodes, the ZrO2-CS-MWCNTs/GCE significantly improves the electrochemical sensing of TDF due to the synergistic effect of the composite. Under optimal conditions, the proposed method has achieved good results in linear range (0.3~30 μM; 30~100 μM) and detection limit (0.0625 μM). Moreover, the sensor has the merits of simple preparation, good reproducibility and good repeatability. The ZrO2-CS-MWCNTs/GCE has been applied to the determination of TDF in serum and urine, and it may be helpful for potential applications of other substances with similar structures.

A simple stability indicating RP-HPLC-DAD method for concurrent analysis of Tenofovir Disoproxil Fumarate, Doravirine and Lamivudine in pure blend and their combined film coated tablets

The main aim of the study was to develop an economical, insightful, accurate and simple RP-HPLC-DAD method with high precision and good sensitivity for concurrent determination of Tenofovir disoproxil fumarate, Doravirine and Lamivudine in blended bulk form and their combined tablet form. A method with Ascentis C18 (150×4.6mm, 5μm) column, mobile phase ratio of 0.1% ortho phosphoric acid and Acetonitrile in 70:30 (v/v), 1mL/min flow rate and detection wavelength of 260nm was highly proficient in effective separation of all three drugs. The developed method was validated in accordance with ICH specifications. The retention times of Doravirine, Lamivudine and Tenofovir disoproxil fumarate observed were 2.4, 2.9, and 3.6min, respectively. The linear responses were observed for Doravirine, Lamivudine and Tenofovir disoproxil fumarate in the range of 12.5-75μg/mL, 75-225μg/mL and 75-225μg/mL, respectively. The limit of detection and quantification values were calculated to be 0.36μg/mL and 0.11μg/mL for Lamivudine, 0.55μg/mL and 1.66μg/mL for Tenofovir disoproxil fumarate and 0.03μg/mL and 0.09μg/mL for Doravirine. The % RSD values of the intra-day and inter-day precision were calculated in the range of 0.134-1.749. The mean percentage recovery of all three analytes was in the range of 98.85-100.18%. The statistical results of the validation parameters ensured that the method was accurate, specific, and precise with good sensitivity. Investigation of analytes under different stressed conditions ensures the stability of analytes reflecting the stability indication of the method. The developed method has high proficiency in separation of Tenofovir disoproxil fumarate, Doravirine and Lamivudine. The degradation products generated due to stress conditions also separated with good resolution. The current method is a stability-indicating assay method consisting of appropriate specificity, accuracy, precision and sensitivity. The developed method has a good potential to be adopted by the pharmaceutical industrial sector.

Simultaneous Determination of Tenofovir Disoproxil Fumarate and Emtricitabine by UV Vierordt’s and UFLC Methods

Simultaneous Determination of Tenofovir Disoproxil Fumarate and Emtricitabine by UV Vierordt’s and UFLC Methods

A new analytical method for determination of tenofovir disoproxil fumarate and emtricitabine in pharmaceutical formulations by RP-HPLC method

A simple, rapid, precise, sensitive and reproducible reverse phase high performance liquid chromatography (RP-HPLC) method has been developed for the quantitative analysis of Tenofovir Disoproxil Fumarate and Emtricitabine in pharmaceutical dosage form. Chromatographic separation of Tenofovir Disoproxil Fumarate and Emtricitabine was achieved on Waters Alliance -2695, by using Luna C18 (250mm x 4.6mm, 5µm) column and the mobile phase containing 0.1% TEA adjusted pH-2.5 with OPA & ACN in the ratio of 60:40 v/v. The flow rate was 1.0 ml/min, detection was carried out by absorption at 261 nm using a photodiode array detector at ambient temperature. The number of theoretical plates and tailing factor for Tenofovir Disoproxil Fumarate and Emtricitabine were NLT 2000 and should not more than 2 respectively. The linearity of the method was excellent over the concentration range 30-450 µg/ml and 20-300 µg/ml for Tenofovir Disoproxil Fumarate and Emtricitabine respectively. The correlation coefficient was 0.999. % Relative standard deviation of peak areas of all measurements always less than 2.0. The proposed method was validated according to ICH guidelines. The method was found to be simple, economical, suitable, precise, accurate & robust method for quantitative analysis of Tenofovir Disoproxil Fumarate and Emtricitabine study of its stability.

A REVIEW ON ANALYTICAL METHODS FOR ESTIMATION OF TENOFOVIR DISOPROXIL FUMARATE AND EMTRICITABINE IN BULK AND PHARMACEUTICAL DOSAGE FORMS

Tenofovir Disoproxil Fumarate and Emtricitabine are very effectively used in the prevention of HIV-1 infections. They are generally administered as tablets. These are Nucleotide Reverse Transcriptase Inhibitors (NtRTIs), an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5′-monophosphate. Emtricitabine and Tenofovir disoproxil fumarate reveals equally prevention of the enzyme that is HIV-1 reverse transcriptase. For determination of Tenofovir disoproxil fumarate and Emtricitabine in bulk and pharmaceutical dosage form, several analytical methods including UV, HPLC, UPLC and HPTLC techniques are reported in literature. For qualitative and quantitative estimation of Tenofovir disoproxil fumarate and Emtricitabine these analytical methods can be used and also for the related degradants in bulk formulations and biological fluid. The present paper illustrates the review on analytical methods which involves the estimation of the antiviral drugs.
 Keywords: Emtricitabine, Tenofovir disoproxil fumarate, UV Spectroscopy, RP-HPLC, UPLC, HPTLC.

The DEVELOPMENT OF A VALIDATED STABILITY INDICATING LC-MS METHOD FOR THE DETERMINATION OF TENOFOVIR DISOPROXIL FUMARATE USING QUALITY BY DESIGN APPROACH

Objective: To develop a validated Liquid Chromatography-Mass Spectrometry (LC-MS) method through Quality by Design (QbD) approach for the determination of tenofovir disoproxil fumarate (tenofovir DF) in bulk, pharmaceutical formulation and stress conditions.
 Methods: The analytical target profile (ATP) was to develop a simple, accurate, precise, specific, and robust method with the Critical Quality Attribute (CQA) being retention time, theoretical plate and peak tailing. Derived from the risk assessment studies, four high-risk factors were screened using resolution V irregular fraction design. Organic modifier strength, flow rate and injection volume were further optimized using Box-Behnken design (BBD). The optimized method condition was validated and applied for the determination of the analyte in pharmaceutical formulation. The stability of the analyte in stress conditions was determined. All experiments were performed using reverse-phase Acquity UPLC BEH C18 (1.7 µm, 1 mm X 50 mm) column coupled in-line with Synapt G2 mass spectrometer in positive electrospray ionization (ESI) mode with electron multiplier analog-to-digital detector.
 Results: Optimized method condition eluted analyte at 3.40 min and the m/z 520 ratified the analyte peak. The method was validated and was found to be specific, linear in the range of 20-100 µg/ml (R2 = 0.9998) with accuracy between 98.71% - 101.17% and precise. The limit of detection and quantification were 5.50 µg/ml and 16.68 µg/ml respectively. Analyte degraded completely in acid and basic environment, however, stable in oxidative and photolytic conditions.
 Conclusion: The validated method developed through the systematic and rational QbD approach bespoke superior quality. The QbD approach not only justified the entire process but also eliminated uncertainties.

Enantiomeric Separation and Quantitation of Tenofovir Disoproxil Fumarate Using Amylose-Based Chiral Stationary Phases by High-Performance Liquid Chromatography

A rapid high-performance liquid chromatography (HPLC) method for chiral purity determination of tenofovir disoproxil fumarate in raw material and pharmaceutical formulations was developed. The (S)-enantiomer appears to be as an impurity and pharmacologically inactive. The effects of various stationary phases, mobile phase composition, and column temperature on enantiomeric separation of tenofovir disoproxil were investigated and optimized. Chromatography resolution of tenofovir disoproxil enantiomers was performed on NUCLEOCEL ALPHA-RP S column (250 × 4.6 mm i.d., 5 μm). The elution was achieved by using 95:5% (υ/υ) methanol—acetonitrile, containing 0.1% triethylamine at a flow rate of 0.8 mL min−1. The ultraviolet (UV) detector was set at 260 nm. Calibration curves were linear in the range of 1–100 μg mL−1 and 0.2–20 μg mL−1 for (R)-tenofovir disoproxil and (S)-enantiomer, respectively. Limits of detection and quantitation for (S)-enantiomer were 0.06 and 0.2 μg mL−1. The run time of analysis was less th...

Development of new spectrophotometric method for estimation of tenofovir disoproxil fumarate using MBTH reagent

A new simple, sensitive and specific procedure has been developed for determination of tenofovir disoproxil fumarate in bulk and pharmaceutical dosage forms using MBTH reagent. The purpose of this analytical validation procedure is to validate it by laboratory experiments to prove that the method meets the minimum standards for laboratory use. 3-methyl-2-bezothiazoline hydrazone reacts with the secondary amine group of tenofovir in the presence of oxidizing agent, ferric chloride. The resulting apple green coloured chromogen when measured spectrophotometrically in visible region (i.e., 400-800nm) shows a maximum absorbance at 626.5nm. This method can be successfully applied for the determination of drug content in pharmaceutical formulations. The results of analysis have been validated statistically.DOI: http://dx.doi.org/10.3329/icpj.v4i4.22620 International Current Pharmaceutical Journal, March 2015, 4(4): 378-381

Development of a validated HPLC method for the determination of tenofovir disoproxil fumarate using a green enrichment process

A MSPE method for the detection of TDF using recoverable NiFe2O4/MWCNT was developed. IL-[C8mim][PF6] can substitute for toxic and hazardous solvents as a green eluent. The proposed method was successfully applied to determine trace TDF in real samples.

Extractive Spectrophotometric Determination of Tenofovir Disoproxil Fumarate Using Acidic Triphenylmethane Dyes

Tenofovir disoproxil fumarate is a nucleotide reverse transcriptase inhibitor that has activity against the hepatitis B and HIV viruses. Three simple and sensitive extractive spectrophotometric methods have been described for the assay of tenofovir disoproxil fumarate either in pure form or in pharmaceutical formulations. The developed methods involve formation of colored chloroform extractable ion-pair complexes of the drugs with triphenylmethane dyes, namely, bromothymol blue (BTB), bromophenol blue (BPB), and bromocresol purple (BCP) in acidic medium. The extracted complexes showed absorbance maxima between 410 and 415 nm. Beer’s law is obeyed in the concentration ranges 1.5–25, 1.0–25, and 1.25–25 μg mL−1 with BTB, BPB, and BCP, respectively. The effectc of concentration of dye, pH, and interference of excipients have been studied and optimized. The limits of detection and quantification have been determined. All three methods are validated as per the guidelines of ICH. The methods have been applied to the determination of drug in commercial tablets and results of analysis were validated statistically through recovery studies.

Selective RP-HPLC DAD method for determination of tenofovir fumarate and emtricitabine in bulk powder and in tablets

A simple and selective liquid chromatographic method was developed for the simultaneous determination of tenofovir disoproxil fumarate (TEN) and emtricitabine (EMT) in combined tablets. The method is based on separation of TEN and EMT on a Zorbax SB-C8 column, 5 μm, 4.6 × 250 mm, with a mobile phase consisting of 50 mM disodium hydrogen phosphate-acetonitrile (50:50, v/v). The mobile phase contains 0.1% triethylamine (TEA) and was adjusted to pH 6.0. Quantification of the analytes is achieved with diode array — ultraviolet detector (DAD-UV) at 260 and 280 nm for TEN and EMT, respectively, based on peak area. Different variables affecting the method were carefully investigated and optimized. Reliability and analytical performance of the proposed method, including linearity, range, precision, accuracy, and detection and quantitation limits, were statistically validated. The high-performance liquid chromatography (HPLC) method was successfully applied for determination of each drug in their binary tablets.

Development of validated stability-indicating simultaneous estimation of Tenofovir disoproxil fumarate and emtricitabine in tablets by HPTLC

AimA simple, accurate, precise and rapid HPTLC methods for simultaneous determination of Tenofovir disoproxil fumarate (TDF) and emtricitabine (ETB) in combined dosage forms. MethodThe method is based on HPTLC separation of the two drugs followed by densitometric measurements of their spots at 276 nm. The separation was carried out on Merck TLC aluminium sheets of silica gel 60F 254 using toluene: ethyl acetate: methanol: acetic acid (6: 4: 3:0.4, v/v/v) as a mobile phase. Stability of TDF and ETB was carried out by forced degradation study. ResultTDF and ETB gave sharp and well defined peak at Rf 0.41 and 0.68, respectively. Calibration curves were linear in range 150–1500 ng/spot and 100–1000 ng/spot for TDF and ETB, respectively. Method was successively applied to tablet formulation. Stability study shows that the chromatograms of samples degraded with acid, base, hydrogen peroxide and light showed well separated spots of pure TDF and ETB as well as some additional peaks at different Rf values. ConclusionThe method is successively applied to pharmaceutical formulation; No chromatographic interferences from the tablet excipients were found. The suitability of this HPTLC method for quantitative determination of the compounds is proved by validation in accordance with the requirements of ICH guidelines.

Development and Validation of UV-Visible Spectrophotometric Baseline Manipulation Method for Simultaneous Quantitation of Tenofovir Disoproxil Fumarate and Emtricitabine in Pharmaceutical Dosage Form

A simple, economical, precise, and accurate new UV-visible spectrophotometric baseline manipulation method for simultaneous determination of tenofovir disoproxil fumarate (TE) and emtricitabine (EM) in combined tablet dosage form has been developed. The method is based on baseline manipulation (difference) spectroscopy where amplitudes at 261 and 289.9 nm were selected to determine TE and EM, respectively, in combined formulation, and distilled water was used as solvent. Both drugs obey Beer’s law in the concentration ranges of 4–20 μg/mL for TE and 6–30 μg/mL for EM. The results of analysis have been validated statistically, and recovery studies confirmed the accuracy of the proposed method which was carried out by following the ICH guidelines.

RP-HPLC method for simultaneous estimation of tenofovir disoproxil fumarate, lamivudine, and efavirenz in combined tablet dosage form

Background: A simple, precise, accurate, and rapid reverse phase-high performance liquid chromatography (RP-HPLC) method with UV-Visible detector has been developed and subsequently validated for the simultaneous determination of tenofovir disoproxil fumarate (TDF), lamivudine (LAMI), and efavirenz (EFV) in their combined tablet dosage form. Materials and Methods: The separation was based on the use of a Kromasil C18 analytical column (150 x 4.6 mm, i.d., 5 μm). The mobile phase consisted of a mixture of 70 volumes of methanol and 30 volumes of 10 mM phosphate buffer (pH 5.0). The separation was carried out at 40°C temperature with a flow rate of 1 ml/min. Results: Quantitation was achieved with UV detection at 254 nm, with linear calibration curves at concentration ranges of 1–6 μg/ml for TDF and LAMI and 2–12 μg/ml for EFV. The recoveries obtained were 99.46-101.36% for LAMI, 99.57-101.42% for TDF, and 99.96-100.87 for EFV. Conclusion: The method was validated according to International conference of harmonisation guidelines in terms of accuracy, precision, specificity, robustness, limits of detection and quantitation, and other aspects of analytical validation.

Stress Studies of Tenofovir Disoproxil Fumarate by HPTLC in Bulk Drug and Pharmaceutical Formulation

A stability-indicating high-performance thin-layer chromatographic (HPTLC) method for determination of tenofovir disoproxil fumarate in bulk drug and in tablet has been developed and validated. The mobile phase selected was chloroform : methanol (9.0 : 1.0, v/v) with ultraviolet (UV) detection at 260 nm. The retention factor was found to be 0.49 ± 0.03 with correlation coefficients of 0.9994 in the range 300–1500 ng/spot and with an accuracy of 99.25%. Method had the potential to determine tenofovir disoproxil fumarate from tablet without any interference, and it was a stability-indicating one.

Spectrophotometric simultaneous determination of Tenofovir disoproxil fumarate and Emtricitabine in combined tablet dosage form by ratio derivative, first order derivative and absorbance corrected methods and its application to dissolution study

Three simple, economical, precise, and accurate methods are described for the simultaneous determination of Tenofovir disoproxil fumarate (TE) and Emtricitabine (EM) in combined tablet dosage form. The first method is ratio derivative spectra, second is first-order derivative spectrophotometry and third is absorption corrected method. The amplitudes at 271.07 and 302.17nm in the ratio derivative method, 224.38 and 306.88nm in the first order derivative method were selected to determine Tenofovir disoproxil fumarate (TE) and Emtricitabine (EM), respectively, in combined formulation. Beer's law is obeyed in the concentration range of 3-21μ/ml for TE and 2-14μ/ml for EM for first two methods and range for third method was 6-30μ/ml of TE and 4-20μ/ml of EM. The percent assay for commercial formulation was found to be in the range 98.91%–101.72% for both the analytes by the proposed three methods. Absorption corrected method was successfully applied to carry out dissolution study of commercial tablet formulation by using USP II dissolution test apparatus. The methods were validated with respect to linearity, precision, and accuracy. Recoveries by proposed methods were found in the range of 99.06 %-101.34 % for both the analytes.

Liquid Chromatography Metabolite Profiling of Tenofovir Disoproxil Fumarate

Liquid Chromatography Metabolite Profiling of Tenofovir Disoproxil FumarateReverse transcriptase inhibitors are the most frequently prescribed agents for HIV infections. This publication presents a validated, highly sensitive and selective isocratic HPLC method for the quantitative determination of tenofovir disoproxil fumarate and its metabolite tenofovir. Detection was performed on a UV detector. The linearity for the calibration curve in the concentration range of 80-20400 ng/mL for tenofovir disoproxil fumarate (TENDF) and 10-2560 ng/mL for tenofovir (TEN) is presented. Inter- and intra-day precision and accuracy of the proposed method were characterised by relative standard deviation (R.S.D.) and percentage deviation, respectively: with both lower than 4% for all analytes. The limit of detection was 33.46 ng/mL for TENDF and 2.10 ng/mL for TEN.

RP‐HPLC Method for the Determination of Tenofovir in Pharmaceutical Formulations and Spiked Human Plasma

A simple reverse‐phase high‐performance liquid chromatographic method for the determination of tenofovir disoproxil fumarate (TDF) in pharmaceutical formulations and human plasma samples has been developed and validated. Piroxicam (PRX) was used as an internal standard. The assay of the drug was performed on a CLC C18 (5 μ, 25 cm×4.6 mm i.d.) with UV detection at 259 nm. The mobile phase consisted of acetonitrile–water mixture in the ratio of 75∶25, and a flow rate of 1 ml/min was maintained. The standard curve was linear over the range of 0.2–10 µg/ml (r 2=0.9966). Analytic parameters have been evaluated. Within‐day and between‐day precision as expressed by relative standard deviation was found to be less than 2%. The method has been applied successfully for the determination of TDF in spiked human plasma samples and pharmaceutical formulations.