Stability‐indicating HPLC method for simultaneous quantification of 14 impurities in excedrin tablet formulations and identification of new impurity by LC–MS in accelerated stability studies

We developed novel stability‐indicating HPLC method for simultaneous estimation of 14 impurities in excedrin tablet, a formulation with a combination of acetaminophen, aspirin, and caffeine. In addition, a new impurity that was generated through degradation of aspirin at high temperatures during the accelerated stability conditions was positively identified and confirmed, using liquid chromatography–mass spectrometry technique. The HPLC method was optimized using the Inertsustain C₁₈, 250 × 4.6 mm, 5.0 μm column, employing simple gradient method. Forced degradation studies were performed under acidic, basic, oxidative and thermal conditions to prove the scope and stability‐indicating the nature of the method. The optimized method was validated as per the International Conference on Harmonization guidelines. The HPLC method showed linearity from LOQ concentration to 21 μg mL^?1. Precision and intermediate precision values were <5% RSD. The validated HPLC method is currently applied for the routine testing of excedrin tablet formulations in quality control laboratories.     

A Simple Approach to Simultaneous Electroanalytical Quantification of Acetaminophen and Tramadol Using a Boron‐doped Diamond Electrode in the Existence of Sodium Dodecyl Sulfate

The present work describes the individual, selective and simultaneous quantification of acetaminophen (ACP) and tramadol hydrochloride (TRA) using a modification‐free boron‐doped diamond (BDD) electrode. Cyclic voltammetric measurements revealed that the profile of the binary mixtures of ACP and TRA were manifested by two irreversible oxidation peaks at about +1.04 V (for ACP) and +1.61 V (for TRA) in Britton‐Robinson (BR) buffer pH 3.0. TRA oxidation peak was significantly improved in the presence of anionic surfactant, sodium dodecyl sulfate (SDS), while ACP signal did not change. By employing square‐wave stripping mode in BR buffer pH 3.0 containing 8×10^?4 mol L^?1 SDS after 30 s accumulation under open‐circuit voltage, the BDD electrode could be used for quantification of ACP and TRA simultaneously in the ranges 1.0–70 μg mL^?1 (6.6×10^?6–4.6×10^?4 mol L^?1) and 1.0–70 μg mL^?1 (3.3×10^?6–2.3×10^?4 mol L^?1), with detection limits of 0.11 μg mL^?1 (7.3×10^?7 mol L^?1) and 0.13 μg mL^?1 (4.3×10^?7 mol L^?1), respectively. The practical applicability of the proposed approach was tested for the individual and simultaneous quantification of ACP and/or TRA in the pharmaceutical dosage forms.     

Development and validation of a generic high‐performance liquid chromatography for the simultaneous separation and determination of six cough ingredients: Robustness study on core–shell particles

A generally applicable high‐performance liquid chromatographic method for the qualitative and quantitative determination of pharmaceutical preparations containing phenylephrine hydrochloride, paracetamol, ephedrine hydrochloride, guaifenesin, doxylamine succinate, and dextromethorphan hydrobromide is developed. Optimization of chromatographic conditions was performed for the gradient elution using different buffer pH values, flow rates and two C₁₈ stationary phases. The method was developed using a Kinetex® C₁₈ column as a core–shell stationary phase with a gradient profile using buffer pH 5.0 and acetonitrile at 2.0 mL/min flow rate. Detection was carried out at 220 nm and linear calibrations were obtained for all components within the studied ranges. The method was fully validated in agreement with ICH guidelines. The proposed method is specific, accurate and precise (RSD% < 3%). Limits of detection are lower than 2.0 μg/mL. Qualitative and quantitative responses were evaluated using experimental design to assist the method robustness. The method was proved to be highly robust against 10% change in buffer pH and flow rate (RSD% < 10%), however, the flow rate may significantly influence the quantitative responses of phenylephrine, paracetamol, and doxylamine (RSD% > 10%). Satisfactory results were obtained for commercial combinations analyses. Statistical comparison between the proposed chromatographic and official methods revealed no significant difference.     

Simultaneous Determination of Acetaminophen, Caffeine, and Chlorphenamine Maleate in Paracetamol and Chlorphenamine Maleate Granules

A simple and rapid HPLC method using phenacetin (PHN) as internal standard has been developed for simultaneous determination of acetaminophen, caffeine, and chlorphenamine maleate in the product compound paracetamol and chlorphenamine maleate granules. Separation and quantitation were achieved on a 250 mm × 4.6 mm, 5 μm particle, C₁₈ column. The mobile phase was methanol 0.05 mol L^?1 aqueous KH₂PO₄ solution, 45:55 (v/v), containing 0.1% triethylamine and adjusted to pH 3.6 by addition of phosphoric acid; the flow rate was 1.0 mL min^?1. Detection of all compounds was by UV absorbance at 260 nm and elution of the analytes was achieved in less than 12 min. The linearity, accuracy, and precision of the method were acceptable to good over the concentration ranges 6.4–153.6 μg mL^?1 for acetaminophen, 5.0–120.0 μg mL^?1 for caffeine, and 9.6–230.4 μg mL^?1 for chlorphenamine maleate.     

Full Validation of a Simple Method for Determination of Catechins and Caffeine in Brazilian Green Tea (Camellia sinensis var. assamica) Using HPLC

This paper describes the validation of an HPLC method for the assay of a green tea brew. The method employs a RP-18 column with water:methanol:ethyl acetate elution and UV detection at 280 nm. Specificity was evaluated using a photodiode array detector. The validation data showed that the assay is specific, accurate, precise, and reproducible for determination of six catechins and caffeine simultaneously. The response was linear over a range of 37–185 μg mL^?1 for caffeine, 99–500 μg mL^?1 for (?)-epigallocatechin (EGC), 20–100 μg mL^?1 for (+)-catechin (C), 30–150 μg mL^?1 for (?)-epicatechin (EC), 150–800 μg mL^?1 for (?)-epigallocatechin gallate (EGCG), 20–105 μg mL^?1 for (?)-gallocatechin gallate (GCG) and 40–205 μg mL^?1 for (?)-epicatechin gallate (ECG) (r > 0.9999 for all compounds). The range of recoveries was 96.12–110.48% according to substances. The RSD values for intra- and inter-day precision studies were <2.07 and <6.65%, respectively. The composition of samples assayed suggests that the summer is the best season for extract a major content of EGCG and caffeine. This assay can be readily utilized as quality controlled method for major green tea compounds.     

Spectrophotometric Determination of Dextromethorphan Hydrobromide and Ketamine Hydrochloride in Pure and Dosage Forms

Three simple, sensitive and accurate spectrophotometric methods have been developed for the determination of dextromethorphan hydrobromide (DEX) and ketamine hydrochloride (KET) in dosage forms. These methods are based on the formation of ion‐pair complexes with bromocresol green (BCG), bromocresol purple (BCP), and bromophenol blue (BPB) in acidic medium. The coloured ion‐pair products are measured at 419, 409 and 417 nm for DEX and at 417, 408 and 416 nm for KET using BCG, BCP and BPB, respectively. Beer's law was obeyed in the range of 2.0–22 μg mL^?1 for DEX and 2.0–16 μg mL^?1 for KET. The composition of the ion‐pair was established by continuous variation and molar ratio methods. The proposed methods were applied successfully for the determination of DEX and KET in dosage forms applying the standard addition technique and compared statistically with the official methods. The molar absorptivity, Sandell sensitivity, detection and quantification limits were also calculated.     

Drug screening in human plasma by cloud-point extraction and HPLC

Cloud-point extraction (CPE) with RP-HPLC/DAD detection was used to develop a screen for six model basic drugs (paracetamol, promazine, amitriptyline, nortriptyline, clomipramine and chlorpromazine) in human plasma. These drugs’ varied hydrophobicities entail different affinities for the micelle-rich phase and CPE extraction efficiencies. Extraction recovery (except paracetamol) was above 80% and reproducibility (RSD%) ranged from 2.88 to 10.26 intraday and from 3.12 to 12.33 interday. The limits of detection were: 0.125 μg mL^?1 (promazine and chlorpromazine), 0.25 μg mL^?1 (amitriptyline and nortriptyline) and 0.5 μg mL^?1 (paracetamol and clomipramine). The method was linear over the ranges: 0.125–1.0 μg mL^?1 (promazine and chlorpromazine), 0.25–1.0 μg mL^?1 (amitriptyline and nortriptyline), 0.5–1.0 μg mL^?1 (clomipramine) and 0.5–10 μg mL^?1 (paracetamol). The procedure is a good alternative to the SPE or LLE sample preparation usually used.     

Inspiration from Old Dyes: Tris(stilbene) Compounds as Potent Gram‐Positive Antibacterial Agents

Herein we describe the preparation and structure‐activity relationship studies on range of stilbene based compounds and their antibacterial activity. Two related compounds, each bearing carboxylic acid moieties, exhibit good activity against several bacterial strains, including methicillin‐resistant Staphylococcus aureus MRSA (ATCC 33592 and NCTC 10442). Compound 10 was most active against Moraxella catarrhalis with minimum inhibitory concentrations (MICs) of 0.12–0.25 μg mL^?1 and against Staphylococcus spp. with MICs ranging from 2–4 μg mL^?1. The derivative 17 showed increased activity with MICs of 0.06–0.25 μg mL^?1 against M. catarrhalis and 0.12–1 against Staphylococcus spp. This level of activity is similar to that reported for S. aureus for antibiotics, such as vancomycin, with MICs of ≤2.0 μg mL^?1 and clindamycin with MICs of ≤0.5 μg mL^?1. As an indicator of toxicity, 17 was tested for its ability to lyse sheep erythrocytes, and showed low haemolytic activity. Such results highlight the value of tris(stilbene) compounds as antibacterial agents providing suitable properties for further development.     

A New HPLC Method for the Simultaneous Determination of Acetaminophen,Phenylephrine, Dextromethorphan and Chlorpheniramine in Pharmaceutical Formulations

Abstract

Acetaminophen, phenylephrine, dextromethorphan, and chlorpheniramine are frequently associated in pharmaceutical formulations against the common cold. A new high performance liquid chromatography (HPLC) method has been developed for the simultaneous determination of these active pharmaceutical ingredients in pharmaceutical formulations. The separation and quantitation were achieved on a 25 cm underivatized silica column using a mobile phase of methanol: water (containing 6.0 g of ammonium acetate and 10 ml of triethylamine per liter, pH adjusted to 5.0 with orthophosphoric acid), 95:5%(v/v). Detection was carried out using a variable wavelength UV-vis detector at 254 nm for acetaminophen, at 220 nm for phenylephrine, and at 227 nm for dextromethorphan and chlorpheniramine. The method showed linearity for the acetaminophen, phenylephrine, dextromethorphan, and chlorpheniramine in the 162.5–650, 2.5–10, 7.5–30, and 1–4 µg/ml ranges, respectively. The intraday and interday RSDs ranged from 0.92 to 1.52%, 1.00 to 1.76%, 1.21 to 1.74% and 1.26 to 1.80% for the acetaminophen, phenylephrine, dextromethorphan, and chlorpheniramine, respectively. Compounds were eluted in a run time of less than 12 min.     

Simple HPLC method for simultaneous determination of acetaminophen, caffeine and chlorpheniramine maleate in tablet formulations

Summary A simple, rapid and accurate, routine-HPLC method is described for simultaneous determination of acetaminophen, caffeine and chlorpheniramine maleate in a new tablet formulation Chromatographic separation of the three pharmaceuticals was achieved on a Hypersil CN column (150×5.0 mm, 5 μm) using a mobile phase comprising a mixture of acetonitrile, an ion-pair solution and tetrahydrofuran (13:14:87, v/v,pH4.5). The flow-rate was changed from 1.0 mL min⁻¹ (in 0≈7.5 min) to 1.8 mL min⁻¹ (after 3.5 min). was complete in <10 min. The method was validated for system suitability, linearity, accuracy, precision, limits of detection and quantitation, and robustness. Linearity, accuracy and precision were found to be acceptable over the ranges 31.6≈315.8 μg mL⁻¹ for acetaminophen, 9.5≈94.6 μg mL⁻¹ for caffeine and 1.4≈13.8 μg mL⁻¹ for chlorpheniramine maleate.     

Simple determination of betaine,l‐carnitine and choline in human urine using self‐packed column and column‐switching ion chromatography with nonsuppressed conductivity detection

A sequential online extraction, clean‐up and separation system for the determination of betaine, l ‐carnitine and choline in human urine using column‐switching ion chromatography with nonsuppressed conductivity detection was developed in this work. A self‐packed pretreatment column (50 × 4.6 mm, i.d.) was used for the extraction and clean‐up of betaine, l ‐carnitine and choline. The separation was achieved using self‐packed cationic exchange column (150 × 4.6 mm, i.d.), followed by nonsuppressed conductivity detection. Under optimized experimental conditions, the developed method presented good analytical performance, with excellent linearity in the range of 0.60–100 μg mL⁻¹ for betaine, 0.75–100 μg mL⁻¹ for l ‐carnitine and 0.50–100 μg mL⁻¹ for choline, with all correlation coefficients (R²) >0.99 in urine. The limits of detection were 0.15 μg mL⁻¹ for betaine, 0.20 μg mL⁻¹ for l ‐carnitine and 0.09 μg mL⁻¹ for choline. The intra‐ and inter‐day accuracy and precision for all quality controls were within ±10.32 and ±9.05%, respectively. Satisfactory recovery was observed between 92.8 and 102.0%. The validated method was successfully applied to the detection of urinary samples from 10 healthy people. The values detected in human urine using the proposed method showed good agreement with the measurement reported previously.     

Simultaneous determination of fifteen multiclass organic pollutants in human saliva and serum by liquid chromatography–tandem ultraviolet/fluorescence detection: A validated method

A quick and inexpensive validated method, based on sample treatment by liquid–liquid microextraction followed by liquid chromatography (LC) coupled with ultraviolet tandem fluorescence detection is proposed for the determination of 15 multiclass pollutants both in serum and in saliva, as a simple and easy to draw matrix. The method was set up and validated according to European guidelines. The compounds of interest include some endocrine‐disrupting chemicals (i.e. bisphenol A, bisphenol B, bisphenol E, bisphenol F, bisphenol AF, bisphenol A diglycidyl ether, bisphenol M, diethylhexyl phthalate, monoethylhexyl phthalate, triclosan and 4‐nonylphenol), as well as other pollutants belonging to the class of volatile organic compounds (2‐chlorophenol, 1,2 dichlorobenzene, 1,2,4,5‐tetrachlorobenzene). The limits of quantifications ranged from 2.28 × 10^?3 μg mL^?1 (bisphenol A diglycidyl ether) to 6.29 μg mL^?1 (diethylhexyl phthalate), while those of detection ranged from 0.068 × 10^?3 μg mL^?1 (bisphenol A diglycidyl ether) to 1.031 μg mL^?1 (diethylhexyl phthalate). To test method suitability, it was applied to real saliva and serum samples of healthy human volunteers and was found to meet the demands of the laboratories handling simple and relatively inexpensive equipment for screening oriented at rapid and reliable contamination assessment of a population.     

Forced degradation studies of clobetasol 17‐propionate in methanol,propylene glycol,as bulk drug and cream formulations by RP‐HPLC

A rapid, simple, stability‐indicating forced degradation study of clobetasol 17‐propionate was conducted using RP‐HPLC. The method was used to analyze clobetasol 17‐propionate in methanol, propylene glycol, and a cream formulation. Isocratic elution of clobetasol and its degradation products was achieved using a Nova‐Pak® 4 μm C₁₈ 150 mm × 3.9 mm id cartridge column and a mobile phase of methanol: water (68:32 v/v) at a flow rate of 0.9 mL min^?1. Quantitation was achieved with UV detection at 239 nm. Nondegraded clobetasol was eluted at a retention time of 6.0 min. Clobetasol 17‐propionate was subjected to different stress conditions viz., acidic, basic, heat, oxidation, light, and neutral hydrolysis. The greatest degradation occurred under strong base and oxidative conditions. Strong base‐degraded clobetasol produced additional peaks at retention times of 1.8, 4.0, 5.0, and 8.0 min and clobetasol oxidation degradation peaks eluted at 2.2 and 24 min. Complete validation was performed for linearity, accuracy, and precision over the concentration range 0.15–15 μg mL^?1. All data were analyzed statistically and this RP‐HPLC method proved to be accurate, precise, linear, and stability indicating for the quantitation of clobetasol 17‐propionate in methanol, propylene glycol, and cream formulations.     

Solid phase extraction with electrospun nanofibers for determination of retinol and α-tocopherol in plasma

A novel packed-fiber solid phase extraction procedure based on electrospun nanofibers for simultaneous determination of vitamins A (retinol) and E (α-tocopherol) in human plasma has been developed. Parameters affecting extraction efficiency were investigated in detail. The limit of detection is 0.01 μg mL^?1 for retinol, and 0.3 μg mL^?1 for α-tocopherol. The linear range is from 0.05 to 2.0 μg mL^?1 for retinol, and from 0.5 to 30 μg mL^?1 for α-tocopherol. The precision (RSD) is <6%, and the relative recovery >90%. The method was applied to analysis of retinol and α-tocopherol in human plasma with satisfactory results.     

Novel Biomedical Sensors for Flow Injection Potentiometric Determination of Creatinine in Human Serum

Coated‐wire (CW) and tubular (Tu) type membrane sensors for creatinine are developed. These consist of creatinine tungstophosphate(CTP), creatinine molybdophosphate (CMP) and creatinine picrolonate (CPC) ion‐pair complexes as electroactive materials dispersed in plasticized poly(vinyl chloride) matrix membranes. Electrochemical evaluation of these sensors under static (batch) mode of operation reveals near‐Nernstian response with slopes of 62.9, 58.1, and 55.2 mV decade^?1 over the concentration range 1×10^?2–5.0×10^?6, 1×10^?2–7.5×10^?5, and 1×10^?2?3.1×10^?5 mol L^?1. The lower detection limits are 0.39, 3.49, and 2.20 μg mL^?1 creatinine with CTP, CMP and CPC membrane based sensors plasticized with o‐NPOE, respectively. Tubular and coated wire CTP membrane sensors are incorporated in flow‐through cells and used as detectors for flow injection analysis (FIA) of creatinine. The intrinsic characteristics of the detectors under hydrodynamic mode of operation in a low dispersion manifold are determined and compared with data obtained under static mode of operation. With 10^?2 mol L^?1 phosphate buffer of pH 4.5 as a carrier solution, the tubular and coated wire CTP detectors exhibit rapid response of 58.9 and 50.7 mV decade^?1 over the concentration range 1×10^?2–1×10^?5 mol L^?1 and detection limits of 0.39 μg mL^?1 and 0.85 μg mL^?1, respectively. Validation of the assay methods with the proposed sensors by measuring the lower detection limit, range, accuracy, precision, repeatability and between‐day‐variability reveals good performance characteristics confirming applicability for continuous determination of creatinine. The sensors are used for determining creatinine in human blood serum at an input rate of 40 samples per hour. No interferences are caused by creatine, most common anions, cations and organic species normally present in biological fluids. The results favorably compare with data obtained using the standard spectrophotometric method.     

Simultaneous Spectrophotometric Determination of Paracetamol and P‐Aminophenol by Using Mean Centering of Ratio Kinetic Profiles

A specific spectrophotometric method was developed for simultaneous determination of paracetamol (PCT) and p‐aminophenol (PAP) in water samples without prior separation steps. The method is based on the mean centering of ratio kinetic profiles. Paracetamol and P‐aminophenol react with Fe(III)/hexacyanoferrate(III) complex and result in the formation of colored complex, i.e. Prussian Blue. The differences in the rate of reaction of PCT and PAP with reagents make their simultaneous determination feasible by using mean centering of ratio kinetic profiles. The experimental parameters, such as reagent concentrations and pH were optimized for getting results with minimum errors. The analytical characteristics of the method such as detection limit, accuracy, precision, relative standard deviation (R.S.D.) and relative standard error (R.S.E.) for the simultaneous determination of binary mixtures of p‐aminophenol and acetaminophen were calculated. The results show that the method was capable of simultaneous determination of 0.5–21.0 μg mL⁻¹ and 0.1–15.0 μg mL⁻¹ of PCT and PAP, respectively. The proposed method was successfully applied to the simultaneous determination of paracetamol and p‐aminophenol in several pharmaceutical products and synthetics mixtures.     

Difference spectrophotemetric assay of mixtures of phenylpropanolamine hydrochloride with guaifensesin or fextromethorphan hydrobromide in olid cough formulations

A difference spectrophotometric method is described for the selective assay of phenylpropanolamine hydrochloride(I) in the presence of guaifenesin(II) or dextromethorphan hydrobromide(III) without prior separation. The method is based on the spectral change upon oxidation of phenylpropanolamine to benzaldehyde by sodium metaperiodate. The difference absorption spectrum is obtained by measuring oxidized against unoxidized phenylpropanolamine. This spectrum exhibits a maximum of 251.5 nm, a minimum at 275 nm and an isosbestic point at 272.5 nm. Absorbance is linear with concentration for 25–100 μg ml^?1 phenylpropanolamine at 251.5 nm. No changes in the spectra of compounds II and III were observed when these compounds were treated with metaperiodate. Guaifenesin and dextromethorphan are assayed by measuring an aliquot of the sample solution against methanol at 281.5 nm and 286 nm, respectively. Phenylpropanolamine does not interfere at these wavelengths. Calibrations are linear over the range 25–125 μg ml^?1 for II and III. Overall recoveries (±SD, n = 5) from simulated tablets were 99.8 ± 2.6% for I and 100.5 ± 0.5% for II; from simulated capsules, the recoveries were 99.2 ± 0.4% for I and 99.6 ± 0.2% for III. The assay was succesfully applied to commercial tablets and capsules containing these compounds.     

LC–MS–MS Method to Simultaneously Determine Six Probe Drugs for CYP450 Isozymes in Human Liver Microsomes

Here, we report a rapid and specific method based on high-performance liquid chromatography coupled with tandem mass spectrometry (LC–MS–MS) capable of quantifying six CYP450-specific probe substrates in human liver microsomal incubation mixtures simultaneously. These analytes were prepared by single-step extraction and detected in one run by switching polarity of electrospray ionization mode three times. Following optimization of the chromatographic conditions, the peaks were well separated, and retention times ranged between 2.0 and 8.4 min. The total run time for a single injection was within 9 min. This method was fully validated over linear range of 18.8–3,000.0 ng mL^?1 for diclofenac, 0.8–3,000.0 ng mL^?1 for dapson, 1.5–3,000.0 ng mL^?1 for dextromethorphan, 2.0–4,000.0 ng mL^?1 for omeprazole, 75.0–3,000.0 ng mL^?1 for chlorzoxazone and 0.8–3,000.0 ng mL^?1 for phenacetin using diazepam as internal standard. Samples were prepared by protein precipitation and analyzed on the LC–MS–MS equipped with ESI interface. For each analyte, inter- and intra-day precision (RSD%) were <15 % and accuracy was within 85–115 %. The specificity, precision, accuracy, stabilities and matrix effect were evaluated.     

Simultaneous Determination of Nickel(II) and Copper(II) by Second‐Derivative Spectrophotometric Method in Micellar Media

A second‐derivative spectrophotometric method based on zero‐crossing over technique is developed in simultaneous determination of copper(II) and nickel(II) ions. Methylthymol blue (MTB) as a chromogenic reagent and cetyltrimethylammonium bromide as a surfactant were used, and measurements were carried out in buffered solution at pH 6 and at a temperature of 25 °C. The amplitude of derivative spectra was measured at wavelengths of 631.9 and 587.7 nm for the simultaneous determination of Ni²⁺ and Cu²⁺, respectively. Linearity was obtained in the range of 0.5–5.0 μg mL^?1 for both ions in the presence of 0.0–5.0 μg mL^?1 of the other ion as an interfering ion. IUPAC detection limits for Cu²⁺ and Ni²⁺ ions were obtained at 0.48 and 0.43 μg mL^?1, respectively. The proposed procedure has been applied successfully for the simultaneous determination of copper and nickel in synthetic binary mixtures and real samples.     

Determination of Labetalol Hydrochloride in Drug Formulations by Spectrophotometry

A validated, selective and sensitive spectrophotometric method has been developed for the determination of labetalol hydrochloride in commercial dosage forms. The method is based on the coupling reaction of positive diazonium ion of 4‐aminobenzenesulfonic acid with phenolate ion of labetalol to form a colored azo compound which absorbs maximally at 395 nm. Under the optimized experimental conditions, the color is stable up to 2 h and Beer's law is obeyed in the concentration range of 0.8–17.6 μg mL^?1 with a linear regression equation of A = 4.84 × 10^?4 + 7.864 × 10^?2 C and coefficient of correlation, r = 0.9999. The molar absorptivity and Sandell's sensitivity are found to be 2.874 × 10⁴ L mol^?1 cm^?1 and 0.013 μg cm^?2 per 0.001‐absorbance unit, respectively. The limits of detection and quantitation of the proposed method are 0.08 and 0.23 μg mL^?1, respectively. The intra‐day and inter‐day precision variation and accuracy of the proposed method is acceptable with low values of standard analytical error. The recovery results obtained by the proposed method in drug formulations are acceptable with mean percent recovery ± RSD of 99.97 ± 0.52 ‐ 100.03 ± 0.63%. The results of the proposed method compared with those of Bilal's spectrophotometric method indicated excellent agreement with acceptable true bias of all samples within ± 2.0%.