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Stability-indicating liquid chromatographic method for valacyclovir
Abstract
A novel stability-indicating high-performance liquid chromatographic assay method was developed and validated for valacyclovir in the presence of degradation products generated from forced decomposition studies. A Hypersil ODS C-18 (250 x 4.6 mm, packed with 5 micron) column in an isocratic mode with the mobile phase - acetonitrile: phosphate buffer (pH- 3.6) (50:50%v/v) was used. The flow rate was 0.8ml/ min and the detection was done at 252 nm. The retention time was found to be 2.850min. The linearity range was found to be 0.5 - 200 mg/ml. The present method is also useful for the estimation of valacyclovir in pharmaceutica l dosage forms. The proposed method was subsequently validated. The method even proved to be affective on application to a stressed marketed formulation.
... calculated using the following formula. [16][17][18][19][20][21][22][23][24] Robustness:Transmittance at a speci c wavelength with a value of one nm is used to measure robustness. At least six measurements were made of the absorbance of a medication known as reference solution at 250, 251, and 252 nm. ...
Background A novel, straightforward, accurate, repeatable, and precise chromogenic UV-visible spectroscopy and bioanalytical technique for measuring valaciclovir in pharmaceutical formulations and bulk. The MBTH reagent and Valaciclovir, in presence of ferric ammonium sulphate, undergo an oxidative condensation/coupling reaction that results in the formation of a green solution with the greatest absorption peak at 618nm. Linearity range of valaciclovir is 10–500µg/ml, and its correlation coefficient is 0.9997. Careful measurement of valaciclovir yielded a value of < 2. Validation of this method is conducted in accordance with ICH recommendationsQ2R1. Enhanced process was designed, verified, and extended to biological material using the protein precipitation extraction method. Results Valaciclovir's detection and quantification limits were 1.5114 µg/mL and 4.58 µg/mL, respectively. Human serum analysis by UV-Visible spectroscopy was created and verified. 1mL serum sample and 1mL of 0.1M was used for protein precipitation, which was vortexed and centrifuged. Standard solutionwhich had standard intensity range of 5–40 µg/mL, required 5.0 minutes to analyze. At 3.177 minutes, valaciclovir was eluted using the described technique. Valaciclovir showed linear behavior in 10–60 µg/ml range. Percentage Accuracy testing revealed that mean recovery was within region of 100%. Limits of quantitation and detection were determined to be 0.070 ng/ml and 0.212 ng/ml, respectively. Conclusion The developed approach was linear, stability indicating, sensitive, rapid, precise, and accurate. As a result, the developed method might be applied to regular quality control of tablets and bulk medications.
... The greater antiviral activity of acyclovir against HSV compared with VZV is due to its more efficient phosphorylation by the viral thymidine kinase. A few analytical methods have been reported for the quantitative determination of Valacyclovir using UV, 1-6 colorimetric, 7 HPTLC, 8 LC-MS 9,10 and Few HPLC methods were reported for the determination of Valacyclovir in pharmaceutical formulations [11][12][13][14][15][16][17][18][19] in biological fluids. [20][21][22][23] The objective of the work is to develop HPLC method for its estimation and validation in bulk and tablet dosage form with good accuracy, simplicity, precision and economy. ...
A simple reverse phase liquid chromatographic method with ultraviolet detector was developed for the accurate determination of Valacyclovir using GracesmartRP18, C18 Column (250 mm × 4.6 mm, 5μm particle size). The mobile phase used for the determination was Methanol: Citric Acid buffer in a ratio of 60: 40 v/v at a flow rate of 1.0 mL per min. Valacyclovir was eluted at 2.2 ± 0.1 min and detected at 254 nm. The method is linear over the concentration range of 10-50 µg/mL with correlation co-efficient r = 0.999. The plate count and tailing factor was found 3847 and 1.24 respectively. The developed method was proved to be robust after extensively validated with different parameters such as Linearity, Precision, Accuracy, Robustness, Ruggedness, Limit of Detection (LOD), Limit of Quantification (LOQ) and specificity. The validated method is definite, meticulous and reproducible and can be used for routine analysis of Valacyclovir in bulk form.
... Literature survey revealed that few spectrophotometrc methods [4][5][6][7][8][9][10][11] , HPLC methods [12][13][14][15][16][17][18] , and LC-MS methods for biological fluids [19][20][21][22][23] are reported in the literature for the determination of valacyclovir in Bulk, pharmaceutical formulations and serum samples. To our knowledge, no article related to the high-performance thin-layer chromatographic (HPTLC) determination of valacyclovir in pharmaceutical dosage forms has been reported in the literature. ...
A simple, sensitive, precise and specific high-performance thin-layer chromatographic (HPTLC) method for the determination of valacyclovir both in bulk drug and pharmaceutical dosage form was developed and validated. The method employed aluminium plates precoated with silica gel G60 F254 as the stationary phase. The solvent system consisted of n-butanol: methanol:Water in the proportion of 3:1:1, v/v/v. This solvent system was found to give compact spots for valacyclovir with Rf value 0.22 ± 0.01. Densitometric analysis of valacyclovir was carried out in the absorbance mode at 254 nm. Linear regression analysis showed good linearity (r 2 =0.998) with respect to peak area in the concentration range of 100-700 ng/spot. The method was validated for precision, limit of detection (LOD), limit of quantitation (LOQ), accuracy and specificity. Statistical analysis proved that the method is repeatable and specific for the estimation of the said drug.
... The greater antiviral activity of acyclovir against HSV compared with VZV is due to its more efficient phosphorylation by the viral thymidine kinase. A few analytical methods have been reported for the quantitative determination of Valacyclovir using UV,[1][2][3][4][5][6]colorimetric,[7]HPTLC,[8]LC-MS[9][10]and Few HPLC methods were reported for the determination of valacyclovir in pharmaceutical formulations[11][12][13][14][15][16][17][18][19]in biological fluids.[20][21][22][23]The objective of the work is to develop HPLC method for its estimation and validation in bulk and tablet dosage form with good accuracy, simplicity, precision and economy. ...
... At pH of 1.84, valacyclovir is only 2% hydrolyzed after a period of 24 hr. The prodrug was stable at low pH and rate of decomposition was accelerated at higher pH [5][6][7] . After oral administration Valacyclovir is rapidly converted to acyclovir and further phospharilated to acyclovir triphosphate. ...
Valacyclovir hydrochloride loaded Ethyl cellulose microcapsules were prepared by the solvent evaporation technique. The process induced the formation of microcapsules with the incorporation efficiency of 80% to 90%. The effect of Ethyl cellulose concentration and conditions was evaluated with respect to entrapment efficiency, particle size, surface characteristics and in vitro release behaviors. Infrared spectroscopic study confirmed the absence of any drug -polymer interaction. Microcapsules matrices showing spherical surface, which was confirmed by scanning electron microscopy study. The mean particle size and entrapment efficiency were found to be varied by changing various formulation parameters. The in vitro release profile could be altered significantly by changing various formulation parameters to give a sustained release of drug from the microcapsules.
... VAL is available as tablet dosage form in market and few HPLC 3-5 methods were reported for the estimation of VAL in pharmaceutical formulations and in biological fluids 6 and one of spectrophotometric 7 method were also reported. There are two stability indicating HPLC 8,9 methods were developed for VAL, but the reported methods were having disadvantages like high flow rate and high retention time and more organic phase and the aqueous phase is not compatible to LC-MS analysis. The proposed HPLC method utilizes economical solvent system as compared with the previous reported methods and is compatible with LC-MS analysis. ...
A simple, specific, accurate reverse phase liquid chromatographic method was developed for the estimation of Valacyclovir (VAL) in bulk and tablet dosage forms. A C18 reverse phase column (Develosil) of 250×4.6mm dimensions and 5 μm particle size with mobile phase containing 0.1% v/v Formic acid: Acetonitrile (90:10 v/v) was used and eluents were monitored at 252 nm. The retention time of VAL was 3.98 min and showed a good linearity in a range of 10-50 μg/mL. The percent assay was 98.9% and mean percentage recovery was found to be 98.02%. The proposed method was validated as per ICH guidelines and successfully applied to the estimation of VAL in tablet formulations.
... Valacyclovir is converted by esterase to active drug acyclovir via hepatic first pass metabolism. 3 Literature survey revealed that few Spectrophotometric methods [4][5][6][7][8][9][10][11] , HPLC methods [12][13][14][15][16][17][18] , and LC-MS methods for biological fluids [19][20][21][22][23] are reported in the literature for the determination of VAL in Bulk, pharmaceutical formulations and serum samples. ...
A chiral high performance liquid chromatographic method was developed and validated for the separation of Valacyclovir drug substance and its related substances V1 (guanine), V2 (acyclovir) and V3 unknown impurity). The Valacyclovir and its impurities were resolved on 150 × 4.0 mm (i.d.), stainless steel, packed with 5μm Daicel Chiral Phase Crownpack CR (+) column at 15°C using 0.1% aqueous Phosphoric acid (85%): Methanol (90:10 V/V) as a mobile phase. A PDA detector set at 254 nm was used for detection. The linearity for related substances was obtained within concentrations ranging from 0.3 to 6μg/mL. The correlation coefficient of Valacyclovir was 0.9997. Relative standard deviations of peak areas from six measurements were always less than 2%. TThe proposed method was found to be suitable and accurate for the quantitative determination of Valacyclovir in bulk drug substance and tablet formulation. Validation parameters showed that the method is specific, accurate, precise and reproducible. The method can be used for routine quality control and stability analysis of Valacyclovir drug substance.
... The absolute bioavailability of acyclovir after oral administration of VA reaches 55% which is relatively higher than that of acyclovir (10-20%) [1,2]. literature review of VA revealed that few analytical methods based on spectrophotometry [3][4][5][6], highperformance liquid chromatography (HPLC) with UV detection [7][8][9][10][11], HPLC with MS detection [12][13], and micellar electrokinetic chromatography [14] were reported. Only one spectrofluoremetric method for the determination of VA in tablets and spiked plasma was recorded [15]. ...
A new, selective and sensitive spectrofluorimetric method was developed and validated for the determination of valacyclovir via derivatization with o-phthalaldehyde in presence of 3-mercaptopropionic acid in alkaline medium. The resulted derivative has a strong blue fluorescence that was measured at 452 nm after excitation at 336 nm in aqueous solution. The reaction conditions were carefully studied and optimized. Under the optimum conditions, the fluorescence intensity was linear over a concentration range of 0.40 – 2.00 μg/mL (R2 = 0.9998) with a detection limit of 0.020 μg/mL. The proposed method was fully validated and effectively applied to the analysis of valacyclovir in pure form and tablets. Statistical comparison of the results obtained by the proposed and reference method revealed no significant difference in the performance of the two methods regarding the accuracy and precision respectively. A proposal for the reaction pathway with o-phthalaldehyde was postulated.
... The oral bioavailability of acyclovir is higher after administration of Valacyclovir relative to acyclovir itself. Literature survey reveals that few methods like high performance liquid chromatography 13 and few spectrophotometric methods [14][15][16] . So there is a need for development of simple and suitable analytical spectrophotometric method for the determination of acyclovir and valacyclovir in bulk and pharmaceutical formulations. ...
Simple, sensitive spectrophotometric methods are presented for the assay of acyclovir and valacyclovir in bulk drug and in tablets. The methods employ Nbromosuccinimide (NBS) as the oxidimetric reagent and dye, methyl orange used as a spectrophotometric reagent. The method involves adding a measured excess of
NBS to acyclovir and valacyclovir in acid medium followed by determination of residual NBS by reacting with a fixed amount of methyl orange and measuring the absorbance at 508 nm. The methods developed were applied to the assay of acyclovir and valacyclovir in commercial tablet formulations and the results were compared statistically with those of a reference method. Acyclovir and valacyclovir showed maximum absorbance at 508 nm with linearity was observed in the concentration range of 1-5 µg mL-1 and 5-10 µg mL
-1 respectively. The relative standard deviations of 0.024 % for acyclovir and 0.018 % valacyclovir were obtained. The accuracy and reliability of the methods were further ascertained by performing recovery tests via standard-addition method. The recoveries of acyclovir and valacyclovir tablets are in the range 99.26 ±0.52, 99.47±0.96 respectively. The proposed method is simple, rapid, precise and convenient for the assay of acyclovir and valacyclovir incommercial tablet preparations.
... Abacavir HIV infection UV Spectrophotometry (Raju et al., 2008) HPLC (Savaser et al., 2007, Ferrer et al., 2004) MALDI-TOF/TOF (Notari et al., 2006) Liquid chromatography/tandem mass spectrometry (Clark et al., 2004) Anodic voltammetry (Uslu and Özkan, 2004) Reversed-phase liquid chromatography (Sparidans et al., 2001, Veldkamp et al., 1999) Electrochemical Determination (Dogan et al., 2008) 11. Valacyclovir Herpes simplex virus types, 1 (HSV-1) and 2 (HSV-2) and vericella zoster UV Spectrophotometry (Rao and Sunil, 2009) High performance liquid chromatography (Palacios et al., 2005) ...
Use of Antiviral drugs has increased during past decade to treat viral diseases. This has resulted in development of resistance of the drug towards the target virus. Antiviral drugs have emerged as a new challenge for medical fraternity and environment in general and researchers in particular. Presence of these drugs has created problems for aquatic organisms and raised questions for their removal from water and wastewater. Antiviral Drugs have attracted attention of general public after the outbreak of the swine influenza virus at the global scale. In the present review paper, occurrence and fate of Antiviral drugs in aquatic bodies and environment have been discussed. Classification of the Antiviral drugs based on the types of disease in which they are used and various detection methods for the analysis of Antiviral drugs have also been reviewed.
... 17 To date, few liquid Kinetic Study of the Alkaline Degradation of Oseltamivir Phosphate and Valacyclovir Hydrochloride using Validated Stability Indicating HPLC chromatographic methods with ultraviolet (UV) detection, [18][19][20][21] photodiode array, 22 fluorescence detection, 22 or with mass spectrometry (MS) detection have been reported. [23][24][25][26][27] A literature review of VA revealed that few analytical methods based on spectrophotometry, [28][29][30] high-performance liquid chromatography (HPLC) with UV detection, 21,[31][32][33][34] HPLC with MS detection, 35,36 and micellar electrokinetic chromatography 37 were reported. The objective of the proposed methods is to develop simple and accurate methods for the estimation of OP and VA hydrochloride in bulk and in pharmaceutical dosage forms by reversed phase (RP)-HPLC. ...
Aqueous alkaline degradation was performed for oseltamivir phosphate (OP) and valacyclovir hydrochloride (VA). Isocratic stability indicating the use of high-performance liquid chromatography (HPLC) was presented for each drug in the presence of its degradation product. The separations were performed using the Nucleosil ODS column and a mobile phase consisting of phosphate buffer (pH = 7), acetonitrile, and methanol 50:25:25 (v/v/v) for OP. For VA separation, a Nucleosil CN column using phosphate buffer (pH = 7) and methanol 85:15 (v/v) was used as a mobile phase. Ultraviolet detection at 210 nm and 254 nm was used for OP and VA, respectively. The method showed high sensitivity concerning linearity, accuracy, and precision over the range 1-250 μg mL(-1) for both drugs. The proposed method was used to determine the drug in its pharmaceutical formulation and to investigate the degradation kinetics of each drug's alkaline-stressed samples. The reactions were found to follow a first-order reaction. The activation energy could also be estimated. International Conference on Harmonisation guidelines were adopted for method validation.
... [8][9][10]. Extensive literature surveys have reported several analytical techniques for the estimation of VCR in both bulk and dosage forms [11][12][13][14][15][16][17][18][19][20][21][22][23]. To the best of our knowledge, the application of the experimental design approach was not found in the development of analytical methods of HPLC for VCR. ...
Impurity profiling has also become an important phase of pharmaceutical research, where both spectroscopic and chromatographic methods find applications. The analytical methodology needs to be very sensitive, specific and precise which will separate and determine the impurity of interest at 0.1% level. Current research reports a validated RP-HPLC method to detect and separate valacyclovir related impurities (Imp-E and Imp-G) using Box Behnken design approach of Response Surface Methodology. Gradient mobile phase (buffer: acetonitrile as mobile phase A and acetonitrile: methanol as mobile phase B) was used. Linearity was found in the concentration range of 50-150 µg/mL. The mean recovery of impurities was 99.9% and 103.2% respectively. The %RSD for the peak areas of Imp-E and Imp-G were 0.9 and 0.1 respectively. No blank interferences at the retention time of impurities suggest the specificity of the method. The LOD values were 0.0024 µg/mL for Imp-E and 0.04 µg/mL for Imp-G and the LOQ values obtained as 0.0082 µg/mL and 0.136 µg/mL respectively for the impurities. S/N ratios in both cases were within specification limits. Proper peak shapes, satisfactory resolution with good retention time suggested the suitability of the method for impurity profiling of valacyclovir related drug substances.
Felodipine (FDP) is a vascular selective L-type calcium channel blocker, in hypertension patients FDP significantly lowers systolic and diastolic blood pressure (BP). It is a lipophilic drug molecule that contains a dihydropyridine ring responsible to show pharmacological activity, it is mainly used to control and prevent essential hypertension. This review article provides a summary of various analytical techniques for determining felodipine in pure form, pharmaceutical formulations, and biological fluids. Various analytical techniques are developed and validated, such as ultraviolet/visible spectrophotometry, high-performance liquid chromatography (HPLC), high-performance thin layer chromatography (HPTLC), and bioanalytical techniques. Estimated validation parameters such as linearity, LOD (Limit of Detection), and LOQ (Limit of Quantification) are discussed for each method. The wavelength of detection (λmax), mobile phase, columns, flow rate, retention time (Rt) and sample preparation techniques are all important quality elements for calculating Felodipine via analytical procedures.
Valacyclovir (VCH) is an antiviral drug, used in the management of viral infections such as herpes simplex and varicella-zoster in humans. It is rapidly converted to acyclovir which has antiviral activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and Varicella-zoster virus (VZV) both in vitro and in vivo. Electrochemical behavior was studied using cyclic voltammetric method, and the analytical application was studied using differential pulse voltammetric technique. The process on the surface of electrode was found to be irreversible and diffusion controlled. The charge transfer coefficient, heterogeneous rate constant, the number of electron transferred and activation parameters were calculated. Possible free radical reaction mechanism taking place on the surface of electrode was proposed. Calibration plot constructed using differential pulse voltammetric technique and applied for quantitative analysis in pharmaceutical and human urine sample. Limit of detection (LOD) and limit of quantification (LOQ) were calculated and found to be 0.028 and 0.09 µM, respectively. The present work describes the electrochemical behavior of an antiviral drug, VCH and its determination in pharmaceutical samples. The method shows the development of a sensor for selective and sensitive determination of VCH.
A rapid RP-HPLC method for determination of Valacyclovir in bulk and pharmaceutical dosage forms. Valacyclovir was found to be degraded under different set of conditions as followed according to ICH guidelines and the degradants so formed along with Valacyclovir are separated by using Hypersil BDS C18 150mm×4.6mm×5μm using mobile phase comprising of mobile phase-A (sodium dihydrogen phosphate monohydrate buffer PH 3.51 with Orthophosphoric Acid) and mobile phase-B (acetonitrile: methanol, 60:40), with a flow rate of 1.5ml/min with a detection wavelength of 254nm with a injection volume of 10μl and the method was validated for specificity, linearity, accuracy, robustness and precision. The obtained results were indicating that the method is selective in analysis of both Valacyclovir in the presence of degradation products formed under various stress conditions.
A novel and quick high-performance thin-layer chromatographic method -densitometric method was developed and validated for quantitative determination of Valacyclovir Hydrochloride. Chromatographic separation of the drugs was performed on precoated silica Tab 60 F254 Merck plates using Toluene: Methanol: Diethylamine (8:1:1 v/v/v).as a mobile phase. A TLC scanner set at 254 nm was used. Valacyclovir Hydrochloride and degradant were satisfactorily resolved with Rf values of 0.28 ± 0.05, 0.65 ±0.05. The method had an accuracy of 99.85% of Valacyclovir Hydrochloride was validated according to ICH guidelines. The percentage recovery ranges from 99-101%. Force degradation of drugs in hydrolysis, oxidation photolysis and thermal stress as per ICH guideline. The drug showed instability in oxide and Heat and Oxide while it remained stable in neutral conditions. The proposed HPTLC method was utilized to investigate of alkaline degradation of VAL.
Two stability- indicating methods were developed and validated for determination of valacyclovir HCL (VAC) in the presence of its degradation product, acyclovir. The first was TLC- densitometric method, in which chloroform: methanol: ammonia (50:14:2 v/v/v) was used as mobile phase. Silica gel 60 F254 was used as a stationary phase and the chromatogram was scanned at 253 nm. Using this chromatographic system, VAC can be readily separated from its degradation product and give compact spot at RF value of (0.55 ± 0.03). The peak area concentration plot is rectilinear over the range 20 - 300 ng band-1. The second method represents the first attempt for spectrofluorimetric determination of VAC. The method was based on the reaction between VAC and 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in an alkaline medium (pH 8.5) to form highly fluorescent product that was measured at 500 nm after excitation at 465 nm. The fluorescence intensity concentration plot is rectilinear over the range 1-10 µg ml-1. The proposed methods were successfully applied for the determination of VAC in its commercial tablets with average percentage recovery of 100.13 ± 0.33 and 98.50 ± 1.75 for TLC- densitometric and spectrofluorimetric methods, respectively without interference from common excipients. The results of the proposed methods were statistically analyzed and found to be in accordance with those given by a reported method. In addition the proposed methods were extended to stability study of VAC, where the drug was exposed to acidic, alkaline, oxidative and photolytic degradation according to ICH guidelines.
Antiviral drugs have been recently recognized as one of the emerging contaminants in the environment. These are discharged after therapeutic use through human excretion. Effluent containing high concentration of antiviral drugs discharged from production facilities is also a cause of concern to nearby aquatic bodies. There is an increased interest in their removal because they are highly bioactive. Some antiviral drugs are resistant to conventional methods of degradation, and there is a risk of development of antiviral resistance in humans and animals if exposed repeatedly for long periods. To date, the potential human, animal, and ecological risks associated with the discharge of these antiviral compounds to the environment are not well documented. This study presents a brief summary on occurrence, ecotoxicological risks, and physicochemical properties of antiviral drugs in the environment. The needs regarding removal, disposal, and treatment of antiviral drugs are also addressed.
A specific, sensitive, simple, and rapid HPLC method has been developed for the determination of valacyclovir (VACL) in raw material, pharmaceutical dosage forms, and human serum, in order to carry out drug dissolution studies from tablets. The chromatographic separation was achieved with acetonitrile: methanol: 0.067 M KH2PO4 (27:20:53, v/v/v) adjusted to pH 6.5 with 3 M NaOH as mobile phase, a Waters Spherisorb C18 column, and UV detection at 244 nm. Etodolac was used as an internal standard. Linearity range was 5-20,000 ng mL(-1). Limit of detection obtained was 0.38 and 0.14 ng mL(-1) in mobile phase and spiked human serum samples, respectively. The described method can be readily applied, without any interferences from the excipients, for the determination of the drug in tablets, human serum samples, and drug dissolution studies.
A Simple, sensitive, spectrophotometric method in UV region has been developed for the determination of valacyclovir in bulk and tablet dosage forms. Valacyclovir is a new antiviral drug, which shows maximum absorbance at 274 nm with apparent molar absorpitivity of 2.69167 × 10 4 L/molcm. Beer's law was obeyed in the concentration range of 5-50 μg/mL. Results of the analysis were validated statistically and by recovery studies.
A simple, rapid, sensitive and precise reverse phase-high performance liquid chromatographic (HPLC) method has been developed for the estimation of valacyclovir in tablets and human serum. In this method, RP-C18 column (150 × 4.6 mm I.D., 5 μm particle size) with mobile phase consisting of acetonitrile and 0.03 M phosphate buffer pH 2.99 in the ratio of 50 : 50 (v/v) in isocratic mode was used. The detection wavelength is 230 nm and the flow rate is 0.8 mL/min. In the range of 0.05-8 μg/mL, the linearity of valacyclovir shows a correlation coefficient of 0.9999. The mean recovery of the drug from the spiked serum solution was found to be 97.82%. The proposed method was validated by determining sensitivity, accuracy, precision and system suitability parameters. The high percentage of recovery indicates that there is no interference from the other serum contents.
A new analytical method was developed together with its validation study, by means of a high resolution liquid chromatography (HPLC) of reverse phase to quantify valacyclovir L‐Valine, ester with 9‐[(2‐hydroxyethoxy)methyl]guanine hydrochloride in tablets. Determination was carried out by means of an ODS C18 column (Microsorb‐MV™100 A, 10 µm, 25 cm × 4.6 mm); the mobile phase consisted of acetic acid in water (1∶1000)∶methanol (70∶30). It was pumped through the chromatographic system at a flow rate of 1.0 mL/min.The UV detector was operated at 254 nm. The validation study was carried out fulfilling the ICH guidelines in order to prove that the new analytical method meets the reliability characteristics, and these characteristics show the capacity of an analytical method to keep, throughout the time, the fundamental criteria for validation: selectivity, linearity, precision, accuracy, and sensitivity. The method is applied during the working day for the quality control of commercial valacyclovir tablets in order to quantify the drug and to check the uniformity content test.
A rapid high-performance liquid chromatographic assay with isocratic elution is developed for the simultaneous quantification of valaciclovir (VACV) prodrug and its active converted compound, acyclovir (ACV), in biological fluids of treated patients. For serum, the samples are deproteinized with perchloric acid in presence of 1-methylguanosine as the internal standard (IS). For urine and dialysis liquid, the samples are diluted with a mobile phase containing the IS, then filtered. VACV, ACV and the IS are separated on a SymmetryShield RP-8 column with acetonitrile-ammonium phosphate buffer as the mobile phase and detected at 254 nm. The chromatographic time is about 12 min. The relative standard deviations (RSD) of VACV and ACV standards are between 0.5 and 3.5%. Most endogenous nucleosides and their metabolites, psychotropic drugs and drugs of abuse are shown not to interfere with this technique. The method has been applied to study the pharmacokinetics of VACV and ACV in serum, dialysis liquid and urine of renal failure patients on continuous ambulatory peritoneal dialysis (CAPD) under oral treatment of VACV.
The stability of valacyclovir hydrochloride in three commonly used syrups was studied.
Triplicate suspensions of valacyclovir (from caplets) in Ora-Sweet (Paddock Laboratories), Ora-Sweet SF (Paddock), and Syrpalta Humco Laboratory) syrups were extemporaneously compounded to yield a final concentration of valacyclovir 50 mg/mL (as the hydrochloride salt). The nine suspensions were stored at 4 degrees C in amber glass bottles. At intervals up to 60 days, the liquids were visually inspected for color change, cloudiness, gas formation, and precipitation, and samples were assayed in duplicate for valacyclovir concentration by stability-indicating high-performance liquid chromatography. Also tested were pH, particle size, and microbial growth.
During the first 21 days of storage, mean valacyclovir concentrations in all liquids were >90% of the initial concentration, but concentrations were <90% by day 21 in some individual samples of suspensions prepared with Ora-Sweet and Ora-Sweet SF. Mean valacyclovir concentrations in the Syrpalta-based suspensions met the 90% cutoff for at least 35 days. Solution pH and particle size remained unchanged in all liquids through day 60, and there were no changes in physical appearance. There was no evidence of microbial growth on the days when microbial growth was tested (0 and 28).
Valacyclovir 50 mg/mL (as the hydrochloride salt) in three oral liquids stored in amber glass bottles at 4 degrees C was stable for at least 21 days when prepared with two of three syrups and for at least 35 days when prepared with the third syrup. All the liquids were free of microbial growth for at least 28 days.
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