A simple and sensitive kinetic spectrophotometric method was developed for the determination of fexofenadine hydrochloride in bulk and pharmaceutical preparations. The method is based on a kinetic investigation of the oxidation reaction of fexofenadine using alkaline potassium permanganate as an oxidizing agent at room temperature. The reaction is followed spectrophotometrically by measuring the increase of absorbance owing to the formation of manganate ion at 610 nm. The initial rate and fixed time (at 15 min) methods are utilized for construction of calibration graphs. All the reaction conditions for the proposed method have been studied. The linearity range was found to be 2.5–50.0
Fexofenadine, (±)-4-[1-hydroxy-4-[4-(hydroxyl diphenylmethyl)-1-piperidinyl]butyl]-alpha, alpha-dimethyl benzene acetic acid, an active metabolite of terfenadine, is a selective histamine H1-receptor antagonist and is clinically effective in the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria as a first-line therapeutic agent, such as loratadine and cetirizine [
Kinetic methods have certain advantages in pharmaceutical analysis regarding selectivity and elimination of additive interferences, which affect direct spectrophotometric methods. The literature is still poor in analytical assay methods based on kinetics for the determination of fexofenadine in dosage forms. Some specific advantages that the kinetic methods possess are as follows: simple and fast methods because some experimental steps such as filtration and extraction are avoided prior to absorbance measurements; high selectivity since they involve the measurement of the absorbance as a function of reaction time instead of measuring the concrete absorbance value; other active compounds present in the commercial dosage forms which may not interfere if they are resisting the chemical reaction conditions established for the proposed kinetic method, and colored and/or turbid sample background which may not possibly interfere with the determination process [
In our study fexofenadine was found to react with permanganate in alkaline medium; the reaction yielded a bluish green manganate with a
A Jasco V-530 UV-VIS spectrophotometer (Japan) with 1 cm quartz cells was used for all absorbance measurements under the following operating conditions: scan speed medium (400 nm/min), scan range 350–700 nm, and slit width 2 nm. Spectra were automatically obtained by Jasco system software. pH measurements were made with Consort C830 (Belgium) with combined glass pH electrode.
All chemicals and reagents used throughout this work were of analytical reagent grade and supplied by Merck (Germany) and solutions were made with doubly distilled water. Fexofenadine hydrochloride (FEX) was obtained from Chem Pharma (India). The purity of FEX was found to be 99.86% according to BP [
Stock solutions,
Aliquots of 2.5–50
Aliquots of 2.5–50
Twenty tablets were weighted accurately and crushed to a fine powder. In the case of capsules, the contents of twenty capsules were completely evacuated from shells. An accurately weighed quantity of the powder equivalent to 25 mg of the cited drug was dissolved in 50 mL of methanol and mixed for about 15 min and then filtered through Whatman filter paper number 40. The methanol was evaporated to dryness. The remaining portion of solution was dissolved in a 100 mL volumetric flask to the volume with double distilled water to achieve a concentration of 0.25 mg mL−1. The general procedure was then followed in the concentration ranges mentioned above.
Potassium permanganate in alkaline medium oxidizes FEX and yields the bluish green color due to the production of manganate ion which is absorbed maximally at 610 nm as shown in Figure
Absorption spectra of (1) 45
The spectrophotometric properties of the colored product as well as the different experimental parameters affecting the color development and its stability were studied and optimized by changing each variable in turn, while keeping all the others constant. The effect of potassium permanganate concentration on the reaction was studied over the range
Effect of 0.01 M KMnO4 or 1.0 M NaOH volume on the absorbance at 610 nm of reaction product of 15
The effect of temperature on the reaction of FEX with KMnO4 in alkaline medium was studied at different values (20–55°C) by continuous monitoring of the absorbance at 610 nm. It was found that the reaction with KMnO4 was not affected by increasing the temperature, and the reaction at laboratory ambient temperature (25±5°C) went to completion within 15 min. The results revealed that increasing the temperature (>55°C
Because the intensity of the color increased at 610 nm with time (Figure
Absorbance-time curve for reaction of FEX with KMnO4 in NaOH medium; CFEX: 2.5–50
The initial rate of reaction would follow a pseudo order rate constant and obeyed the following rate equation:
Calibration plot of logarithm rate of the reaction against logarithm molar concentration of FEX for initial rate method.
The logarithm of the absorbance of reaction versus time for each concentration of FEX studied over the concentration range of 2.5–50.0
Calibration plot of FEX for rate constant method.
Reaction rate data were recorded for different FEX concentrations in the range 30.0–50.0
Calibration plot of FEX for fixed absorbance method.
At preselected fixed time, the absorbance of bluish green colored solution containing varying amounts of FEX was measured at 25°C and 610 nm. Calibration graphs were constructed by plotting the absorbance against the initial concentration of FEX at fixed time 0–30 min. The regression equations, correlation coefficients, and linear ranges are given in Table
Regression equations for FEX at fixed time and 25°C.
Time (min) | Regression equation | Correlation coefficient | Linear range ( |
---|---|---|---|
0 |
|
0.9971 | 2.5–50.0 |
5 |
|
0.9981 | 2.5–50.0 |
10 |
|
0.9993 | 2.5–50.0 |
15 |
|
0.9997 | 2.5–50.0 |
20 |
|
0.9991 | 2.5–50.0 |
25 |
|
0.9968 | 2.5–50.0 |
30 |
|
0.9943 | 2.5–50.0 |
It is clear that the slope increases with time and the most acceptable value of
After optimizing the reaction conditions, the fixed time was applied to the determination of FEX in pure form over the concentration range 2.5–50.0
Analytical characteristics of the fixed time (15 min) method.
Parameters | FEX |
---|---|
|
610 |
Beer’s law range ( |
2.5–50.0 |
Ringbom optimum concentration range ( |
10.0–40.0 |
Detection limit ( |
0.055 |
Quantification limit ( |
0.183 |
Molar absorptivity (L mol−1 cm−1) | 1.22 × 104 |
Stoichiometric relationship, FEX : KMnO4 | 1 : 1 |
Sandell’s sensitivity ( |
0.088 |
Regression equationa |
|
Correlation coefficient, |
0.9998 |
The minimum level at which the investigated compound can be reliably detected (limit of detection, LOD) and quantified (limit of quantitation, LOQ) was determined experimentally for fixed time (15 min) method. The LOD was expressed as the concentration of drug that generated a response to three times of the signal to-noise (S/N) ratio, and the LOQ was 10 times of the S/N ratio. The LOD of FEX attained as defined by IUPAC [
The accuracy and precision of the proposed method were carried out by six determinations at four different concentrations. Percentage relative standard deviation (RSD%) as precision and percentage recovery as accuracy of the suggested methods were calculated and shown in Table
Accuracy and precision for the determination of FEX in bulk powder by the proposed initial rate and fixed time methods.
Method | FEX, |
RSD% |
Confidence limit |
Recovery% | ||
---|---|---|---|---|---|---|
Taken | Founda | SD | ||||
Initial rate | 5.00 | 5.01 | 0.12 | 2.39 | 5.01 ± 0.13 | 100.20 |
20.00 | 20.20 | 0.20 | 0.99 | 20.20 ± 0.22 | 101.00 | |
35.00 | 34.90 | 0.28 | 0.80 | 34.90 ± 0.31 | 99.71 | |
50.00 | 50.13 | 0.14 | 0.28 | 50.13 ± 0.15 | 100.26 | |
|
||||||
Fixed time | 5.00 | 5.04 | 0.13 | 2.58 | 5.04 ± 0.15 | 100.80 |
20.00 | 20.14 | 0.30 | 1.49 | 20.14 ± 0.34 | 100.70 | |
35.00 | 35.00 | 0.32 | 0.91 | 35.00 ± 0.36 | 100.00 | |
50.00 | 50.31 | 0.36 | 0.71 | 50.31 ± 0.40 | 100.62 |
The stoichiometry of the reaction was studied adopting the limiting logarithmic method [
Stoichiometry of the reaction between FEX and alkaline potassium permanganate adopting limiting logarithmic method. (a)
The proposed techniques were applied to the tablets and capsules. The ingredients in the tablets and capsules did not interfere in the experiments. The applicability of the proposed methods for the assay of fexofenadine hydrochloride in formulations was examined by analyzing various formulations and the results tabulated in Table
Determination of FEX in different pharmaceutical formulations by the proposed and official methods.
Formulation | Label claim | % Founda ± SD | ||
---|---|---|---|---|
Proposed methods |
Official method [ | |||
Initial rate | Fixed time | |||
Allergy stopb | 60 mg/Cap | 100.75 ± 0.19 | 101.04 ± 0.21 | 100.79 ± 0.13 |
|
|
| ||
|
|
|||
120 mg/Tab | 101.06 ± 0.20 | 100.12 ± 0.18 | 101.05 ± 0.15 | |
|
|
| ||
|
|
|||
180 mg/Tab | 99.98 ± 0.18 | 100.60 ± 0.20 | 99.78 ± 0.14 | |
|
|
| ||
|
|
|||
|
||||
Fexofenadinec | 60 mg/Cap | 100.27 ± 0.15 | 101.00 ± 0.13 | 100.84 ± 0.11 |
|
|
| ||
|
|
|||
|
||||
Fenadind | 120 mg/Tab | 101.96 ± 0.13 | 100.26 ± 0.14 | 99.69 ± 0.12 |
|
|
| ||
|
|
|||
180 mg/Tab | 100.95 ± 0.20 | 101.08 ± 0.23 | 100.52 ± 0.18 | |
|
|
| ||
|
|
bSupplied by Pharmasyr, Syria; csupplied by Ibn-Alhaytham, Syria; dsupplied by BPI, Syria.
The developed kinetic spectrophotometric method for the determination of fexofenadine hydrochloride in bulk and pharmaceutical formulations was sensitive, accurate, and precise. The limits of detection and quantitation were 0.055 and 0.183
There is no kind of financial gain between the authors and the mentioned corporations and identities inside the paper.