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Kinetic spectrophotometric method for the determination of perindopril erbumine in pure and commercial dosage forms
⁎Corresponding author. Tel.: +91 571 2703515. cht17nr_amu@yahoo.com (Nafisur Rahman)
-
Received: ,
Accepted: ,
This article was originally published by Elsevier and was migrated to Scientific Scholar after the change of Publisher.
Peer review under responsibility of King Saud University.
Abstract
A kinetic spectrophotometric method has been developed for the determination of perindopril erbumine in pure and commercial dosage forms. The method is based on the reaction of drug with potassium permanganate in alkaline medium at room temperature (30 ± 1 °C). The reaction was followed spectrophotometrically by measuring the increase in absorbance with time at 603 nm and the initial rate, fixed time (at 8.0 min) and equilibrium time (at 90.0 min) methods were adopted for constructing the calibration graphs. All the calibration graphs are linear in the concentration range of 5.0–50.0 μg/ml. The limits of detection for initial rate, fixed time and equilibrium time methods were 0.752, 0.882 and 1.091 μg/ml, respectively. The activation parameters such as Ea, ΔH‡, ΔS‡ and ΔG‡ were also determined for the reaction and found to be 60.93 kJ/mol, 56.45 kJ/mol, 74.16 J/K mol and −6.53 kJ/mol, respectively. The variables were optimized and the proposed methods are validated as per ICH guidelines. The method has been further applied to the determination of perindopril erbumine in commercial dosage forms. The analytical results of the proposed methods when compared with those of the reference method show no significant difference in accuracy and precision and have acceptable bias.
Keywords
Spectrophotometry
Perindopril
Commercial dosage forms
1 Introduction
Perindopril erbumine is chemically known as (2S, 3aS, 7aS)-1-[(S)-N-[(S)-1-carboxybutyl] alanyl] hexahydro-2-indolinecarboxylic acid, 1-ethylester, compound with tert-butylamine (1:1). It is a pro drug and metabolized in vivo by hydrolysis of the ester group to form perindoprilat, the biologically active metabolite. It is an angiotensin converting enzyme inhibitor (ACE) (Laubie et al., 1984) used to reduce the cardiovascular risk of individuals with hypertension or post myocardial infarction and stable coronary disease. The effectiveness of perindopril as an antihypertensive drug has been demonstrated in various clinical trials (Lees and Reid, 1987; Herpin et al., 1989). ACE inhibitors reduce blood pressure by inhibiting the enzyme which catalyses the conversion of angiotensin I into angiotensin II. Decreased plasma angiotensin II leads to an increase in plasma rennin activity and a decrease in aldosterone. Studies in animals and humans suggest that specific and competitive suppression of the rennin–angiotensin–aldosterone system is the main mechanism by which blood pressure is reduced. This drug is officially listed in the monograph of British Pharmacopoeia (London, 2004), which describes a potentiometric titration procedure for its assay in formulations. In order to assure the quantity of perindopril in pharmaceutical preparations, few analytical methods have been reported in the literature for the determination of perindopril such as gas chromatography (Lin et al., 1996), high performance liquid chromatography (HPLC) and reversed phased - HPLC (Medenica et al., 2007; Rani and Sekaran, 2009; Chaudhary et al., 2010; Pathak et al., 2011; Raju and Rao, 2011), capillary electrophoresis (Hillaert and Bossche, 2000), atomic absorption spectrophotometry (Abdellatef et al., 1999) and LC–MS/MS (Jain et al., 2006; Nirogi et al., 2006).
Methods have also been reported based on spectrophotometry for its quantification in commercial dosage forms (Abdellatef et al., 1998; Abdellatef, 1998; Erk, 2001; Rahman et al., 2006; Rani et al., 2009; Rahman and Rahman, 2011; Sharma and Sharma, 2011; Sridevi et al., 2012; Rahman et al., 2012; Suresh and Sagar, 2012). Kinetic-based spectrophotometric methods are not widely applied, although they offer the advantage of eliminating additive interferences, which probably affects other methods such as titrimetry and direct spectrophotometric methods. These methods used in drug analysis have gained special interest as they offer many advantages over regular analytical techniques. These advantages include improved selectivity and a decrease of interferences caused by coloured or turbid samples during testing.
The proposed method describes a validated kinetic spectrophotometric method for the determination of perindopril erbumine in pure and commercial dosage forms. The method is based on the reaction of drug with potassium permanganate in alkaline medium at room temperature (30 ± 1 °C) and subsequently the rate of appearance of the green coloured product was measured at 603 nm. The initial rate, fixed time and equilibrium time methods are followed for the determination of perindopril erbumine in commercial dosage forms.
2 Experimental
2.1 Apparatus
All spectrophotometric measurements were made on spectronic 20 D+ spectrophotometer (Milton Roy, USA). A water bath shaker (NSW 133, New Delhi, India) was used to control the heating temperature.
2.2 Materials and reagents
Perindopril erbumine was kindly supplied as a gift sample by Glenmark Pharmaceuticals Ltd. Mumbai, India and used without further purification. Commercial tablets of perindopril erbumine such as Coversyl- 2.0® (SERDIA Pharmaceuticals India Ltd.) and Perigard- 2.0® (Glenmark Pharmaceuticals (Zoltan) Ltd., India) were purchased from local pharmacy shop.
4 × 10−1 M sodium hydroxide (GR Grade, Merck Limited, Mumbai, India) solution was prepared in doubly distilled water.
9 × 10−3 M potassium permanganate (GR Grade, Merck Limited, Mumbai, India) solution was also prepared in doubly distilled water.
2.3 Standard test solution
A 2.264 × 10−3 M solution of drug by weighing 0.1 g in 100 ml was prepared in doubly distilled water. The solution was stable for at least five days keeping at room temperature (30 ± 1 °C) when protected from direct sun light.
2.4 Recommended procedures for the determination of perindopril erbumine
2.4.1 Initial rate method
Aliquots of 0.05–0.5 ml of 2.264 × 10−3 M containing 50–500 μg of perindopril erbumine were pipetted into a series of 10 ml standard flasks. To each flask, 2.5 ml of 0.40 M NaOH and 9 × 10−3 M potassium permanganate were added successively and then diluted with distilled water at room temperature (30 ± 1 °C). The contents of each flask were mixed well and measured the increase in absorbance as a function of time at 603 nm. The initial rate of the reaction (ν) at different concentrations was evaluated by measuring the slope of the tangent to the absorbance-time plot. The calibration graphs were obtained by plotting the initial rate of reaction (ν) versus the molar concentration of the perindopril erbumine (C). The amount of the drug was calculated either from the calibration curve or regression equation.
2.4.2 Fixed time method
A fixed time of 8.0 min was selected for this method. At this preselected fixed time, the absorbance of each sample of drug solution was measured at 603 nm against a reagent blank prepared similarly except drug. The calibration curve was obtained by plotting the absorbance against the initial concentration of perindopril erbumine. The amount of the drug was computed either from calibration curve or regression equation.
2.4.3 Equilibrium time method
The equilibrium reaction condition was achieved at 90.0 min and at this time, the absorbance of each sample of drug solution was measured at 603 nm against a reagent blank prepared similarly except drug. The calibration graph was constructed by plotting the absorbance against the initial concentration of perindopril erbumine and the concentration of the drug was calculated either from calibration graph or corresponding regression equation.
2.5 Procedure for determination of perindopril erbumine in commercial dosage forms
To determine the content of perindopril in commercial dosage forms, the contents of 25 tablets were weighed and finely powdered. A portion of the powder equivalent to 50 mg of active ingredient was weighed accurately, stirred well with 20 ml doubly distilled water and allowed to stand for 10 min. The residue was filtered on Whatmann No. 42 filter paper (Whatman International Limited, Kent, UK) and washed with distilled water. The residue was washed well with doubly distilled water for complete recovery of drug and was further diluted to give a final concentration of 1 mg/ml. An aliquot of the diluted solution was analysed for perindopril content following the recommended procedure.
2.6 Limits of detection and quantitation
According to the International Conference on Harmonisation (ICH) guidelines (Ermer, 2001), the following expressions are used to evaluate LOD and LOQ. where S0 and b are standard deviation and slope of the calibration line, respectively.
3 Results and discussion
The absorption spectrum of potassium permanganate solution in the alkaline medium exhibits an absorption band peaking at 530 nm. The course of the reaction starts on the addition of alkaline potassium permanganate solution to the solution of pure perindopril erbumine resulting in the shift of absorption band peaking at 603 nm. This is all due to the formation of manganate ion, in the presence of drug. The intensity of the coloured product increases with time and therefore a kinetic approach can be exploited for the spectrophotometric determination of perindopril erbumine in drug formulations.
The limiting logarithmic method (Rose, 1964) was followed by performing two sets of the experiments to establish the stoichiometric ratio between perindopril erbumine and potassium permanganate. In the first set of experiment, the concentration of perindopril erbumine was varied keeping a constant concentration of KMnO4 while in the second set, the concentration of KMnO4 varied, keeping the constant concentration of perindopril erbumine. Log A versus log [Perindopril erbumine] or [KMnO4] (Fig. 1a and b) was plotted to calculate the slope of the respective line to determine the order of reaction of the drug with respect to KMnO4 or vice versa. The slope was found to be unity in the first case and it was two in magnitude in the second case thus confirming the molar combining ratio of 1:2 between perindopril erbumine and potassium permanganate. Hence, the results indicated that the two moles of potassium permanganate were consumed by one mole of perindopril erbumine. In this reaction, perindopril undergoes hydrolysis in the presence of NaOH producing ethyl alcohol. The resulting ethyl alcohol is oxidized by KMnO4/OH− whereby the permanganate is reduced to the manganate ion, which is a coloured species. Therefore, based on the literature background and our experimental findings, a reaction mechanism was proposed and shown in Scheme 1. The proposed mechanism was further proved by treating ethyl alcohol with potassium permanganate in alkaline medium under the same conditions whereby the coloured product with same absorption spectrum, was produced.![Plot of stoichiometric ratio between perindopril and KMnO4 (a) log A vs log [Perindopril erbumine] and (b) log A vs log [KMnO4].](/content/184/2017/10/1_suppl/img/10.1016_j.arabjc.2012.12.017-fig1.png)
Plot of stoichiometric ratio between perindopril and KMnO4 (a) log A vs log [Perindopril erbumine] and (b) log A vs log [KMnO4].
3.1 Optimization of variables
The effect of temperature on the initial rate of reaction was studied at 303, 308, 313 and 318 K. It was observed that perindopril erbumine reacts faster with potassium permanganate with an increase in temperature. At higher temperatures, the reaction product may decompose and reproducibility was not better. To avoid this and for the sake of good results, the optimum temperature of 303 K was selected for the determination process.
The effect of the KMnO4 concentration on the initial rate of reaction (ν) was studied in the range of 1.80 × 10−4–2.43 × 10−3 M. The initial rate of reaction was increased with increase in the concentration of KMnO4 and became constant at 1.80 × 10−3 M and remained as such up to 2.43 × 10−3 M. Therefore, a concentration of 2.25 × 10−3 M was used as an optimum value for the assay procedure. The results are summarized in Table 1.
| [KMnO4] (mol/l) | [NaOH] (mol/l) | Initial rate of reaction, υ (mol/l s) | |
|---|---|---|---|
| KMnO4 | NaOH | ||
| 1.80 × 10−4 | 0.80 × 10−2 | 8.33 × 10−5 | 3.38 × 10−4 |
| 5.40 × 10−4 | 2.40 × 10−2 | 2.50 × 10−4 | 4.00 × 10−4 |
| 9.00 × 10−4 | 4.00 × 10−2 | 3.85 × 10−4 | 5.00 × 10−4 |
| 1.26 × 10−3 | 5.60 × 10−2 | 5.00 × 10−4 | 6.00 × 10−4 |
| 1.44 × 10−3 | 6.40 × 10−2 | 6.53 × 10−4 | 6.25 × 10−4 |
| 1.80 × 10−3 | 8.00 × 10−2 | 7.63 × 10−4 | 7.00 × 10−4 |
| 1.89 × 10−3 | 9.20 × 10−2 | 7.63 × 10−4 | 7.63 × 10−4 |
| 1.98 × 10−3 | 9.60 × 10−2 | 7.63 × 10−4 | 7.63 × 10−4 |
| 2.07 × 10−3 | 1.00 × 10−1 | 7.63 × 10−4 | 7.63 × 10−4 |
| 2.25 × 10−3 | 1.08 × 10−1 | 7.63 × 10−4 | 7.63 × 10−4 |
| 2.43 × 10−3 | 1.20 × 10−1 | 7.63 × 10−4 | 7.63 × 10−4 |
The effect of concentration of NaOH on the initial rate of reaction was also studied. The ν value increased with increase in the concentration of NaOH up to 9.2 × 10−2 M, after which further increase in the concentration of NaOH resulted in no change in the initial rate of reaction. Thus, the concentration of 1.00 × 10−1 M was found to be optimum in a volume of 10.0 ml.
4 Analytical parameters and method validation
All kinetic parameters were performed under pseudo-first order conditions at 30 ± 1 °C. The initial rates of the reaction were determined from absorbance-time plot (Fig. 2) by measuring the slopes of the initial tangent to the absorbance-time curves and are summarized in Table 2. The kinetic equation for the reaction of perindopril erbumine in the presence of potassium permanganate in alkaline medium is written as:
Absorbance-time plot for reaction of perindopril with KMnO4 in alkaline medium: 2.25 × 10−3 M KMnO4 and (a) 1.13 × 10−5 (b) 2.26 × 10−5 (c) 4.53 × 10−5 (d) 6.79 × 10−5 (e) 9.06 × 10−5 and (f) 1.13 × 10−4 M Perindopril erbumine.
| [Perindopril erbumine] (mol/l) | Initial rate of reaction, υ (mol/l s) |
|---|---|
| 1.13 × 10−5 | 7.92 × 10−5 |
| 2.26 × 10−5 | 1.53 × 10−4 |
| 4.53 × 10−5 | 3.07 × 10−4 |
| 6.79 × 10−5 | 4.60 × 10−4 |
| 9.06 × 10−5 | 6.13 × 10−4 |
| 1.13 × 10−4 | 7.63 × 10−4 |
The order with respect to perindopril erbumine was determined from the plot of logarithm of initial rate of reaction (log ν) versus logarithm of molar concentration of perindopril erbumine (log C) and was found to be unity. Thus, the hydrolysis of perindopril erbumine would obey the pseudo first order reaction and equation (II) reduced to
To evaluate the apparent activation parameters, the reaction rate was studied at 303, 308, 313 and 318 K at [perindopril erbumine] = 2.26 × 10−5 M, [KMnO4] = 2.25 × 10−3 M and [NaOH] = 1.00 × 10−1 M. The Arrhenius plot of ln kobs. versus
was found to be linear (ln k = ln A -
) with correlation coefficient (r2) of 0.9998 ((Fig. 3). Activation energy (Ea) can be calculated from the slope
of the Arrhenius plot and found to be 60.93 kJ/mol. The Eyring plot of ln kobs./T versus
was linear
with correlation coefficient (r2) of 0.9993 (Fig. 4). The values of ΔH‡ and ΔS‡ were evaluated from the slope (−ΔH‡/R) and intercept [ln (kb/h) + ΔS‡/R] of Eyring plot and found to be 56.45 kJ/mol and 74.16 J/K mol, respectively. The value of Gibbs free energy (ΔG‡) of activation of the reaction product was found to be −6.53 kJ/mol.
Arrhenius plot of lnk vs 1/T at 303, 308, 313 and 318 K: Perindopril erbumine (1.13 × 10−5–1.13 × 10−4 M) with initial concentration of KMnO4 (2.25 × 10−3 M) and NaOH (0.1 M) for activation energy (Ea).
Eyring plot of ln (k/T) versus 1/T at 303, 308, 313 and 318 K: Perindopril erbumine (1.13 × 10−5–1.13 × 10−4 M) with initial concentration of KMnO4 (2.25 × 10−3 M) and NaOH (0.1 M) for ΔH‡ and ΔS‡.
In the fixed time method, the absorbance of the coloured product formed due to the reduction of KMnO4 was recorded at a preselected fixed time for different concentrations of perindopril erbumine. The results indicated a linear increase in absorbance with time and hence, determination can be done in a narrow range of time. The calibration graphs were constructed by plotting the absorbance against the initial concentrations of perindopril erbumine at a fixed time of 2, 4, 6, 8 and 10 min. The important parameters of these calibration curves are reported in Table 3. It is clear from Table 3 that the most acceptable values of linearity, intercept, limit of detection and quantitation were obtained at a fixed time of 8 min. Therefore, the fixed time of 8 min was selected as the optimum time for the determination of perindopril erbumine in commercial dosage forms.
| Parameters | Fixed-time method | Equilibrium time method | ||||
|---|---|---|---|---|---|---|
| 2 min | 4 min | 6 min | 8 min | 10 min | ||
| Beer’s law limit (μg/ml) | 5.0–50.0 | 5.0–50.0 | 5.0–50.0 | 5.0–50.0 | 5.0–50.0 | 5.0–50.0 |
| Regression equation | A = −9.45 × 10−4 + 2.03 × 10−3 C | A = 4.16 × 10−4 + 3.83 × 10−3 C | A = 5.75 × 10−3 + 5.21 × 10−3 C | A = 4.47 × 10−3 + 6. 81 × 10−3 C | A = 2.41 × 10−3 + 8.07 × 10−3 C | A = 1.56 × 10−1 + 1.53 × 10−2 C |
| So | 6.03 × 10−4 | 1.18 × 10−3 | 1.86 × 10−3 | 1.82 × 10−3 | 2.49 × 10−3 | 5.06 × 10−3 |
| Sa | 4.69 × 10−4 | 9.17 × 10−4 | 1.45 × 10−3 | 1.42 × 10−3 | 1.94 × 10−3 | 3.93 × 10−3 |
| Sb | 1.54 × 10−2 | 3.02 × 10−3 | 4.47 × 10−3 | 4.67 × 10−3 | 6.40 × 10−3 | 1.30 × 10−2 |
| Correlation coefficient (r2) | 0.9999 | 0.9999 | 0.9998 | 0.9999 | 0.9999 | 0.9999 |
| Detection limit (μg/ml) | 0.9802 | 1.0167 | 1.1781 | 0.8819 | 1.0182 | 1.0914 |
| Quantitation limit (μg/ml) | 2. 9704 | 3.0809 | 3.5700 | 2.6725 | 3.0855 | 3.3071 |
| Variance, (μg/ml) | 3.63 × 10−7 | 1.39 × 10−6 | 3.46 × 10−6 | 3.31 × 10−6 | 6.20 × 10−6 | 2.56 × 10−5 |
S0 is the standard deviation of the calibration line.
In the equilibrium time method, the absorbance of green coloured solution was measured after attaining the equilibrium (at 90 min) for different concentrations of perindopril erbumine. However, this method requires longer time of analysis in comparison to the fixed time method. The linear regression equation and other statistical parameters of this method were summarized in Table 3.
4.1 Selectivity
Selectivity of the method was ascertained by analysing standard perindopril in the presence of common excipients such as lactose, magnesium stearate, cellulose and silicon dioxide. The methods show no interference from the excipients.
4.2 Accuracy and precision
The accuracy and precision of the proposed methods were established by measuring the content of perindopril erbumine at three different concentration levels on each day as well as on five consecutive days. The intra day assay (or the daily precision) was performed by measuring five independent analyses at 10.0, 30.0 and 50.0 μg/ml concentration levels within one day and inter day assay (or within day precision) was done at the same specified levels of concentration by measuring five replicate analyses on five consecutive days (Table 4). The results of standard deviation, relative standard deviation and mean recoveries obtained by intra day and inter day precisions for initial rate, fixed time and equilibrium fixed time methods are acceptable and can be considered to be very satisfactory.
| Proposed methods | Amount (μg/ml) | Recovery (%) | RSDa (%) | SAEb | C.L.c | |
|---|---|---|---|---|---|---|
| Taken | Found ± SDa | |||||
| Initial rate method | ||||||
| Intra day assay | 10.0 | 10.008 ± 0.066 | 100.08 | 0.660 | 0.030 | 0.082 |
| 30.0 | 29.997 ± 0.059 | 99.99 | 0.197 | 0.027 | 0.074 | |
| 50.0 | 50.006 ± 0.051 | 100.01 | 0.102 | 0.023 | 0.064 | |
| Inter day assay | 10.0 | 10.001 ± 0.094 | 100.01 | 0.937 | 0.042 | 0.116 |
| 30.0 | 29.998 ± 0.065 | 99.99 | 0.216 | 0.029 | 0.081 | |
| 50.0 | 49.997 ± 0.057 | 99.99 | 0.114 | 0.026 | 0.071 | |
| Fixed time method | ||||||
| Intra day assay | 10.0 | 9.999 ± 0.065 | 99.99 | 0.645 | 0.029 | 0.080 |
| 30.0 | 30.004 ± 0.123 | 100.02 | 0.410 | 0.055 | 0.153 | |
| 50.0 | 49.975 ± 0.123 | 99.95 | 0.246 | 0.055 | 0.153 | |
| Inter day assay | 10.0 | 10.004 ± 0.197 | 100.04 | 1.969 | 0.088 | 0.245 |
| 30.0 | 29.975 ± 0.167 | 99.92 | 0.559 | 0.075 | 0.208 | |
| 50.0 | 50.004 ± 0.147 | 100.01 | 0.294 | 0.066 | 0.182 | |
| Equilibrium time method | ||||||
| Intra day assay | 10.0 | 9.999 ± 0.103 | 99.99 | 1.033 | 0.046 | 0.128 |
| 30.0 | 30.013 ± 0.085 | 100.04 | 0.284 | 0.038 | 0.106 | |
| 50.0 | 49.987 ± 0.055 | 99.97 | 0.109 | 0.025 | 0.068 | |
| Inter day assay | 10.0 | 9.999 ± 0.065 | 99.99 | 0.654 | 0.029 | 0.081 |
| 30.0 | 29.995 ± 0.140 | 99.99 | 0.465 | 0.062 | 0.173 | |
| 50.0 | 50.013 ± 0.085 | 100.03 | 0.170 | 0.038 | 0.106 | |
Performing recovery experiments through standard addition method also checked the validity of the proposed methods. For this, a known amount of the pure drug was added to preanalysed dosage forms at two concentration levels by measuring five replicate analyses following the recommended procedures for the determination of active drug. The results are summarized in Table 5, which showed excellent recoveries (99.95%–100.10%) with low values of relative standard deviations (0.15%–0.84%). It is also clear from the data that no interference from the common excipients used in tablets was observed.
| Formulations | Initial rate method | Recovery (%) | SAE | C.L. | Fixed time method | Recovery (%) | SAE | C.L | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Amount (μg/ ml) |
Amount (μg/ ml) |
|||||||||||
| Taken | Added | Found ± SDa | Taken | Added | Found ± SDa | |||||||
| Coversyl 2.0® (SERDIA) | 10.0 | 10.0 | 19.999 ± 0.062 | 99.99 | 0.028 | 0.077 | 10.0 | 10.0 | 19.990 ± 0.167 | 99.95 | 0.075 | 0.208 |
| 10.0 | 25.0 | 34.996 ± 0.051 | 99.99 | 0.023 | 0.063 | 10.0 | 25.0 | 34.997 ± 0.123 | 99.99 | 0.055 | 0.153 | |
| Perigard 2.0® (Glenmark, Zoltan) | 10.0 | 10.0 | 20.008 ± 0.079 | 100.04 | 0.035 | 0.098 | 10.0 | 10.0 | 20.019 ± 0.123 | 100.10 | 0.055 | 0.153 |
| 10.0 | 25.0 | 34.996 ± 0.060 | 99.99 | 0.027 | 0.075 | 10.0 | 25.0 | 35.026 ± 0.232 | 100.08 | 0.104 | 0.288 | |
4.3 Evaluation of bias
The point and interval hypothesis tests have been performed to compare results of the proposed methods (with those of the reference method at 95% confidence level (Table 6). The test method is considered acceptable when its true mean is within ± 2.0% of that of the reference methods. This can be written as which can be generalized to where θL and θU are lower and upper acceptance limits, respectively which were calculated from the following quadratic equation (Acceptable methods, 1992).
| Formulations | Initial rate method | Fixed time method | Equilibrium time method | Reference method | ||||
|---|---|---|---|---|---|---|---|---|
| Recovery (%) | RSD (%) | Recovery (%) | RSD (%) | Recovery (%) | RSD (%) | Recovery (%) | RSD (%) | |
| Coversyl 2.0® (SERDIA) | 99. 99 | 0.31 | 100.10 | 0.61 | 99.99 | 0.45 | 99.94 | 0.38 |
| θL = 0.994 | θU = 1.006 | θL = 0.989 | θU = 1.007 | θL = 0.992 | θU = 1.006 | |||
| t = 0.228 | F = 1.503 | t = 0.497 | F = 2.576 | t = 0.185 | F = 1.402 | |||
| Perigard 2.0® | 100.04 | 0.39 | 99. 95 | 0.84 | 99.90 | 0.52 | 99. 99 | 0.37 |
| (Glenmark, Zoltan) | θL = 0.993 | θU = 1.007 | θL = 0.989 | θU = 1.011 | θL = 0.992 | θU = 1.009 | ||
| t = 0.208 | F = 1.111 | t = 0.100 | F = 5.071 | t = 0.310 | F = 1.97 | |||
Theoretical t- (ν = 8) and F-values (ν = 4, 4) at 95% confidence level are 2.306 and 6.39, respectively θL and θU are within the acceptable limits of ±2%.
5 Applicability of the proposed methods
The initial rate, fixed time and equilibrium time methods were successfully applied to the determination of perindopril erbumine in commercial dosage forms. The results of the proposed methods were compared with those of the reference method (Abdellatef, 1998) using point and interval hypothesis tests and are summarized in Table 6. The calculated t- (paired) and F- values at 95% confidence level do not exceed the theoretical ones indicating no significant differences between the performance of the proposed methods and the reference method. A bias of ± 2%, which is based on recovery experiments, is permissible by The Canadian Health Protection Branch (Acceptable methods, 1992). Therefore, the acceptable limit lies within ϕL = 0.98 and ϕU = 1.02. It is evident from Table 6 that the true bias of all samples of drug is smaller than ± 2% and thus confirming that the proposed methods are reliable with acceptable recovery.
6 Conclusions
The proposed kinetic method is sensitive with a simple calibration system that does not require any laborious clean up procedure prior to analysis and performed at room temperature (30 ± 1 °C). Moreover the present technique has the advantage of using inexpensive and easily available low cost reagents and therefore can be frequently used in the laboratories of research, hospitals and pharmaceutical industries. The proposed methods can be used as alternative methods to reported ones for routine determination of perindopril erbumine in the pure form and in commercial dosage forms.
Acknowledgement
The authors are thankful to the Glenmark Pharmaceutical Limited, Mumbai, India for providing the gift sample of pure perindopril erbumine.
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