Analytical Spectrophotometric Study of Enalapril Maleate in Raw Material and Tablets Formulations
Saad Antakli, Leon Nejem, Rayyan Khoja
Department of Chemistry, Faculty of Science, University of Aleppo, Syria
*Corresponding Author E-mail: antakli@scs-net.org
ABSTRACT:
Spectrophotometric method was developed and applied for the determination of enalapril maleate (ENP) in raw material and tablets formulations. This new method was applied to determine (ENP) in several Syrian trademark drugs such as: Enapril and Noropresh. Spectrophotometric method depended on reducing iron III to iron II by (ENP), which reacted with 1-10 phenanthrolin to form iron II:1-10 phenanthrolin complex. This complex was determined at maximum wavelength 510 nm. Linearity range was to be between 10-90 µg/mL. Regression analysis showed a good correlation coefficient R2 = 0.9993. The limit of detection (LOD) and limit of quantification (LOQ) were 1.78 and 5.40 µg/mL respectively. The proposed method was successfully applied to analysis of (ENP) in Syrian trademark drugs. All studied samples showed that the drug levels were conformed to United State Pharmacopeia (USP) legislation.
KEYWORDS: Enalapril Maleate, Spectrophotometric method.
INTRODUCTION:
Enalapril maleate (ENP) is an angiotensin-converting enzyme (ACE) inhibitor and is one of the leading drugs in the world as an anti hypertensive agent belonging to class1. Enalapril maleate (S)-1-[N-[1-(ethoxycarbonyl)-3-phenylpropy1]-L-alanyl]-L-proline hydrogen maleate.
An ACE inhibitor is used in the treatment of hypertension and heart failure. It is also used to reduce the incidence of coronary ischemic events, including myocardial infarction2. It is a pro-drug without direct biological activity which is rapidly absorbed after oral administration and de-esterified in vivo to its active metabolite enalaprilat diketopiperazine derivative (DKP) and has little pharmacologic activity until hydrolyzed in the liver to enalaprilat. Enalapril maleate is an off-white crystalline powder3.
ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. The beneficial effects of enalapril in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system. Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decrease aldosterone secretion4.
Several methods have been successfully applied to determine (ENP) as: spectrophotometric1,2,5,6, and derivative spectrophotometric methods7. Chromatographic methods have been used for (ENP) analysis as high performance liquid chromatography (HPLC)8, reverse phase high performance liquid chromatography (RP-HPLC)3,9, capillary electro phoresis10, micro emulsion liquid chromatography11, liquid chromatography–tandem mass spectrometry12. Square-wave voltammetric13, multiple pulse amperometric detection14. Atomic absorption spectrometric based on ternary complex formation with copper (II), eosin and enalapril15, nuclear magnetic resonance16 and infrared spectrometry17.
The aim of this work is to develop a simple and accurate spectrophotometric method for the determination of (ENP) Fig.1, in different Syrian trademark drugs by UV/Vis spectrophotometry.
Fig. 1: Enalapril maleate.
MATERIALS AND METHODS:
Apparatus:
All spectral measurements were carried out using a T80+ UV/V spectrophotometer PG instrument Ltd (UK) connected to computer, quartz cells 1 cm. Uultrasonic bath (Daihan), and stirrer Velp Scientifica (Europe).
Chemical Regents:
Methanol from Adra (Syria), standard synthetic of enalapril maleate from Zhejiang Huahai pharmrceutical Co., LTD purity 99.4% (China), acetic acid from Surechem products LTD (Britain), ferric chloride anhydrous from Himedia laboratories Pvt LTD (India), 1-10 phenanthrolin from Merck (Germany) and Bi-distilled water.
Stock Standard Preparation:
Stock solutions (1000 µg /mL) of enalapril maleate were prepared by dissolving an appropriate weight of pure material in methanol. Taking the purity of the material on consideration, the concentration became (1006 µg / mL).
Calibration Curve:
To construct the calibration curve, five standard solutions ranging between 10-90 µg /mL of enalapril maleate in methanol were prepared and the absorbance was measured five times for each solution.
Sample Preparation:
Two Syrian trademark products with three different doses for each were studied:
· 20 tablets of Enapril (5 mg) sample were powdered and an accurate weight equivalent to ten tablets, dissolved in methanol, then solution has been stirred for 30 minutes. After that the solution was transferred into a 50 mL volumetric flask and adjusted to volume with the methanol then we have taken 0.5 mL from this solution directly to prepare the sample solutions.
· 20 tablets of Enapril (10 mg) sample were powdered and accurate weight equivalent to five tablets was dissolved in methanol, then solution has been stirred for 30 minutes. After that the solution was transferred into a 50 mL volumetric flask and adjusted to volume with the methanol then we have taken 0.5 mL from this solution directly to prepare the sample solutions.
· 20 tablets of Enapril (20 mg) sample were powdered and an accurate weight equivalent to two and half tablets was dissolved in methanol, then solution has been stirred for 30 minutes. After that the solution was transferred into a 50 mL volumetric flask and adjusted to volume with the methanol then we have taken 0.5 mL from this solution directly to prepare the sample solutions.
· 20 tablets of Noropresh (5 mg) sample were powdered and an accurate weight equivalent to ten tablets was dissolved in methanol, then solution has been stirred for 30 minutes. After that the solution was transferred into a 50 mL volumetric flask and adjusted to volume with the methanol then we have taken 0.5 mL from this solution directly to prepare the sample solutions.
· 20 tablets of Noropresh (10 mg) sample were powdered and an accurate weight equivalent to five tablets was dissolved in methanol, then solution has been stirred for 30 minutes. After that the solution was transferred into a 50 mL volumetric flask and adjusted to volume with the methanol then we have taken 0.5 mL from this solution directly to prepare the sample solutions.
· 20 tablets of Noropresh (20 mg) sample were powdered and an accurate weight equivalent to two and half tablets was dissolved in methanol, then solution has been stirred for 30 minutes. After that the solution was transferred into a 50 mL volumetric flask and adjusted to volume with the methanol then we have taken 0.5 mL from this solution directly to prepare the sample solutions.
All samples were prepared by take 1 mL of acetic acid (10 M), 1.5 mL of Iron (III) chloride 12.5x 10-3 mol/L, 0.5 mL of sample solution and 3.25 mL of 1,10-phenanthroline (2x10-2 M) in 10 mL and completed to 10 mL by bi-distillated water.
RESULTS AND DISCUSSION:
The measurement of (ENP) concentration in raw material and tablets formulation was achieved by reducing iron III to iron II by (ENP):
Enalapril Maleate
Fe+3 ---------------------------> Fe+2
The result iron II reacted with 1-10 phenanthrolin to form iron II :1-10 phenanthrolin complex. Absorption spectrum of the result formed complex was recorded within a wavelength range of 350–600 nm against the blank (all the addition constituents without enalapril malrate), as can be seen Fig. 2, the complex was determined by direct measurement of absorbance at λmax = 510 nm.
Fig. 2: Spectrum of iron III -1-10 phenanthrolin complex for(90 µg/mL) of Enalapril maleate.
The reaction between iron II and 1-10 phenanthrolin leading to complex formation is presented in Fig.3.
Fig. 3: Iron III -1-10 phenanthrolin complex.
Effect of Heating Time:
We studied the effect of the heating time at the convenient temperature degree 95ºC during heating time interval 10 min, for an enalapril maleate sample of 70 µg/mL. Absorbance continued to increase until 90 min, then the absorbance stayed constant, Fig. 4. So the heating time for 90 min was to be chosen at temperature 95ºC as analysis condition.
Fig. 4: Effect of heating time for (70 µg/mL) of Enalapril maleate.
Effect of iron (III) chloride concentration:
To study the Iron (III) chloride concentration influence on the colored solution, we prepared a series of 10 mL volumetric flasks containing each 0.7 mL of (ENP) 2x10-3 mol/L, 1 mL of acetic acid 10 mol/L and between (0.3 – 1.8 mL) of Iron (III) chloride 12.5 x 10-3 mol/L, then added 3.25 mL of 1,10-phenanthroline 2x 10-2 mol/L for each volumetric flask and completed to 10 mL by bi-distillated water. The result solutions were put at 95 ºC for 90 minutes in water bath. The absorbance at 510 nm was determined for every added Iron (III) chloride volume against the blank (all the addition constituents without enalapril malrate). It was found that the completed colored complex formation was after 1.2 mL of Iron (III) chloride solution, so addition of 1.5 mL of Iron (III) chloride solution is equivalent to concentration 18.75 x 10-4 mol/L witch was chosen in our study as it is shown in Fig.5.
Fig. 5: Effect of Iron (III) chloride concentration for (70 µg/mL) of Enalapril maleate.
Effect of 1,10-phenanthroline concentration:
To study the 1, 10-phenanthroline concentration influence on the colored solution, we made a series of 10 mL volumetric flasks containing each 0.7 mL of (ENP) 2 x10-3 mol/L, 1 mL of acetic acid 10 mol/L, 1.5 mL of Iron (III) chloride 12.5x10-3 mol/L and then added between (1 –4 mL) of 1,10-phenanthroline 2x10-2 mol/L for each volumetric flask, and completed to 10 mL by bi-distillated water. The result solutions were put at 95 ºC for 90 minutes in water bath. The absorbance at 510 nm was determined for every added of 1,10-phenanthrolin volume against the blank. It was found that the completed colored complex formation was after 3 mL of 1,10-phenanthroline solution so addition of 3.25 mL of 1, 10-phenanthroline solution is equivalent to concentration 6.5x10-3 mol/L was chosen as it is shown in Fig.6.
Fig. 6: Effect of 1, 10-Phenanthroline concentration for (70 µg/mL) of Enalapril maleate.
Effect of acetic acid:
We studied the complex in acid medium because the iron ions will be precipitated in alkaline medium. The absorbance complex was constant in acetic acid for all assays, however, the addition of HCl, H3PO4, H2SO4, HNO3, HCOOH solutions in place of acetic acid lead to form the complex with weaker absorption than acetic acid addition. We found that best sequence and the optimal concentrations to give highest absorbance was to be: acetic acid 10 M, iron (III) chloride 12.5 x 10-3, (ENP) 1000 µg/mL, 1, 10-Phenanthrolin 2 x 10-2 M, (ENP) 0.7 µg/mL 2 x 10-3 M.
Table1: Added volumes to prepare the samples.
|
Solutions |
Added volume (mL⁄10 mL) |
Concentration |
|
Acetic acid |
1 (10 M) |
1 M |
|
Iron (III) chloride |
1.5 (12.5x10-3 M) |
18.75 x10-4 M |
|
ENP |
0.7 (1000 µg/mL) |
70 µg/mL |
|
1,10-Phenanthroline |
3.25 (2x10-2 M) |
6.5x10-3 M |
The solution has adjusted to 10 mL by bi distillated water.
VALIDATION:
The validity of the proposed method was assessed by accuracy (reported as recovery percentage), precision (reported as RSD %), linearity (evaluated by regression equation), limit of detection (LOD) and limit of quantification (LOQ).
Linearity:
The linearity curve was traced for five representing standard concentrations ranging from 0.1 mL to 0.9 mL that correspond the range 10-90 µg/mL of enalapril maleate which were transferred into a series of 10 mL volumetric flasks. To each flask 1 mL of acetic acid (10 M), 1.5 mL of ferric chloride (12.5x10-3 M) and 3.25 mL of 1-10 phenanthrolin (2x10-2 M), then the volume was made up to the mark with bi-distilled water. The resulting solution was heated for 90 min at 95 ºC. The absorbance of orange reddish colored complex was measured at 510 nm against the blank, Figs. 7and 8.
Fig. 7: spectra of (ENP): C1: 10 µg/mL, C2: 30 µg/mL, C3: 50 µg/mL, C4: 70 µg/mL, C5: 90 µg/mL.
Fig. 8: Calibration curve for (ENP). n = 5 for each concentration.
Limit of Detection (LOD) and Limit of Quantification (LOQ):
LOD and LOQ were calculated and presented in Table 1 using the following equations18:
10 × SD
LOQ =------------------
m
3.3 × SD
LOD =--------------------
m
Where SD is the standard deviation of y-intercepts (a) of regression lines and (b) is the slope of the equitation of calibration curve, y = a + b x.
Table2: Statistical data for calibration graphs.
|
Analyte |
λ max (nm) |
Linearity rang µg/mL |
Correlation coef. (R2) |
LOD µg/mL |
LOQ µg/mL |
|
ENP |
510 |
10 – 90 |
0.9993 |
1.78 |
5.40 |
Accuracy and precision:
To determine the precision and accuracy of the proposed methods, five replicate determinations were carried out on three different concentrations of standards (ENP). The validation results are shown in Table 3.
Table 3: Accuracy and precision for enalapril maleate determination.
|
Theoretical concentration (μg/mL) |
*Observed concentration (μg/mL) |
Precision (RSD %) |
Accuracy (%) |
|
30 |
29.93 |
1.74 |
99.07 |
|
50 |
50.67 |
2.51 |
101.34 |
|
70 |
70.43 |
1.07 |
100.61 |
Precision (RSD %) = (standard deviation/mean concentration) ×100.
Accuracy (%) = (observed concentration/theoretical concentration) ×100.
* Five separate determinations were performed and calculated the mean.
RECOVERY:
The recovery was studied by three addition standards for every product. Table 4 presents the recoveries results for the six Syrian trademark drugs.
Table 4: Recoveries for the six drugs.
|
RSD % |
SD % |
Recovre % |
Total Found µg/mL |
Addedµg/mL |
Sample µg/mL |
Product |
|
|
99.22 |
2.40 |
2.35 |
98.10 |
44.73 |
20 |
25.11 |
Enapril 5 mg |
|
1.91 |
1.93 |
100.90 |
50.34 |
25 |
25.11 |
||
|
1.32 |
1.30 |
98.67 |
54.71 |
30 |
25.11 |
||
|
98.18 |
1.87 |
1.86 |
99.90 |
45.95 |
20 |
25.97 |
Enapril 10 mg |
|
2.30 |
2.22 |
96.52 |
50.10 |
25 |
25.97 |
||
|
1.30 |
1.28 |
98.13 |
55.41 |
30 |
25.97 |
||
|
99.75 |
2.65 |
2.61 |
98.60 |
44.82 |
20 |
25.10 |
Enapril 20 mg |
|
1.34 |
1.34 |
100.04 |
50.11 |
25 |
25.10 |
||
|
1.36 |
1.37 |
100.60 |
55.28 |
30 |
25.10 |
||
|
99.43 |
2.32 |
2.30 |
99.30 |
44.86 |
20 |
25.00 |
Noropresh 5 mg |
|
1.82 |
1.81 |
99.52 |
49.88 |
25 |
25.00 |
||
|
1.12 |
1.11 |
99.47 |
54.84 |
30 |
25.00 |
||
|
99.79 |
2.76 |
2.77 |
100.45 |
45.11 |
20 |
25.02 |
Noropresh 10 mg |
|
2.13 |
2.12 |
99.60 |
49.92 |
25 |
25.02 |
||
|
1.63 |
1.62 |
99.33 |
54.82 |
30 |
25.02 |
||
|
101.03 |
1.25 |
1.28 |
102.30 |
45.66 |
20 |
25.20 |
Noropresh 20 mg |
|
1.35 |
1.36 |
101.00 |
50.45 |
25 |
25.20 |
||
|
1.15 |
1.15 |
99.80 |
55.14 |
30 |
25.20 |
||
|
98.18 – 101.03 |
Range of Recovery Average % |
||||||
Application of the proposed method for estimation in two Syrian tablets formulation drugs:
The developed method was applied for quantitative determination for (ENP) in different Syrian tablets formulation drugs. The samples were prepared as described in the section of samples preparation and analyzed. Quantitative analysis was done by using calibration curves. The obtained results are summarized in Table 5,6 for six different Syrian trademark drugs.
The dosages of (ENP) were conformed to USP legislation.
Tables 5, 6 present the determination results of (ENP) in six Syrian drugs for five different batches for each: (Enapril 5 mg, 10 mg and 20 mg, Noropresh 5 mg, 10 mg and 20 mg).
Table 5: Results of (ENP) in Enapril (5, 10, 20 mg) for five different batches.
|
Enapril 5 mg |
||||||
|
No. of batches |
Result dose mg/tab |
SD mg/tab |
RSD % |
Per % |
||
|
1 |
5.03 |
0.09 |
1.79 |
100.60 |
||
|
2 |
5.07 |
0.12 |
2.37 |
101.40 |
||
|
3 |
5.12 |
0.17 |
3.32 |
102.40 |
||
|
4 |
4.99 |
0.13 |
2.61 |
99.80 |
||
|
5 |
4.86 |
0.09 |
1.85 |
97.20 |
||
|
Range mg/tab |
4.86 - 5.12 |
|||||
|
Range Per % |
97.20 - 102.40 |
|||||
|
Enapril 10 mg |
||||||
|
No. of batches |
mg/tab |
SD mg/tab |
RSD % |
Per % |
||
|
1 |
10.05 |
0.23 |
2.29 |
100.50 |
||
|
2 |
9.99 |
0.22 |
2.20 |
99.90 |
||
|
3 |
10.05 |
0.19 |
1.89 |
100.50 |
||
|
4 |
10.04 |
0.17 |
1.69 |
100.40 |
||
|
5 |
10.16 |
0.25 |
2.46 |
101.60 |
||
|
Range mg/tab |
9.99 - 10.16 |
|||||
|
Range Per % |
99.90 - 101.60 |
|||||
|
Enapril 20 mg |
||||||
|
No. of batches |
Result dose mg/tab |
SD mg/tab |
RSD % |
Per % |
||
|
1 |
19.83 |
0.36 |
1.82 |
99.15 |
||
|
2 |
19.71 |
0.22 |
1.12 |
98.55 |
||
|
3 |
20.05 |
0.27 |
1.35 |
100.25 |
||
|
4 |
20.03 |
0.21 |
1.05 |
100.15 |
||
|
5 |
20.12 |
0.21 |
1.04 |
100.60 |
||
|
Range mg/tab |
19.71 - 20.12 |
|||||
|
Range Per % |
98.55 - 100.60 |
|||||
Table 6: Results of (ENP) in Noropresh (5, 10, 20 mg) for five different batches.
|
Noropresh 5 mg |
|||||||
|
No. of batches |
Result dose mg/tab |
SD mg/tab |
RSD % |
Per % |
|||
|
1 |
5.07 |
0.06 |
1.25 |
101.40 |
|||
|
2 |
5.09 |
0.18 |
3.54 |
101.80 |
|||
|
3 |
5.12 |
0.11 |
2.15 |
102.40 |
|||
|
4 |
5.15 |
0.13 |
2.52 |
103.00 |
|||
|
5 |
5.20 |
0.13 |
2.50 |
104.00 |
|||
|
Range mg/tab |
5.07 - 5.20 |
||||||
|
Range Per % |
101.40 - 104.00 |
||||||
|
Noropresh 10 mg |
|||||||
|
No. of batches |
Result dose mg/tab |
SD mg/tab |
RSD % |
Per % |
|||
|
1 |
10.15 |
0.13 |
1.28 |
101.50 |
|||
|
2 |
10.10 |
0.13 |
1.29 |
101.00 |
|||
|
3 |
10.19 |
0.16 |
1.57 |
101.90 |
|||
|
4 |
10.14 |
0.15 |
1.48 |
101.40 |
|||
|
5 |
10.19 |
0.14 |
1.37 |
101.90 |
|||
|
Range mg/tab |
10.10 - 10.19 |
||||||
|
Range Per % |
101.00 - 101.90 |
||||||
|
Noropresh 20 mg |
|||||||
|
No. of batches |
Result dose mg/tab |
SD mg/tab |
RSD % |
Per % |
|||
|
1 |
20.32 |
0.39 |
1.92 |
101.60 |
|||
|
2 |
20.16 |
0.17 |
0.84 |
100.80 |
|||
|
3 |
20.07 |
0.23 |
1.15 |
100.35 |
|||
|
4 |
20.08 |
0.20 |
1.00 |
100.40 |
|||
|
5 |
20.19 |
0.20 |
0.99 |
100.95 |
|||
|
Range mg/tab |
20.07 - 20.32 |
||||||
|
Range Per % |
100.35 - 101.60 |
||||||
According to USP legislation, the tablets must contain not less than 90.00 percent and not more than 110.00 percent of labelled amount of C20H28N2O5.C4H4O419. So the obtained results are conformed to USP legislation
CONCLUSION:
Enalapril maleate dose was estimated in two Syrian trademark drugs (Enapril 5 mg, 10 mg and 20 mg, Noropresh 5 mg, 10 mg and 20 mg) by simple spectrophotometric method. Enalapril maleate determined by reducing of iron III to iron II by (ENP). After that iron II 1-10 phenanthrolin complex will be formed. This complex could be determined by visible spectrophotometry at maximum wavelength 510 nm. The proposed method of (ENP) determination is accurate, simple, sensitive and easy. Recoveries study assures that the auxiliary ingredient in the different studied trademark drugs didn't have any interferences on the analysis of the enalapril maleate in tablets formulations.
ACKNOWLEDGEMENT:
The Ministry of High Education in Syria financially and technically supported this work through department of Chemistry, Faculty of Science, University of Aleppo, Syria.
CONFLICT OF INTEREST:
The authors declare no conflict of interest.
REFERENCES:
1. M Manoranjani, K Kamala Karuna. UV-visible Spectroscopic Estimation and Validation of Enalapril maleate in Bulk and pharmaceutical Dosage Forms. 2011; pp. 1651-1656.
2. Sayed sh. Alaa A. and. Hany O. Spectrophotometric Microdetermination of Some Antihypertensive Drugs in Pure Form and in Pharmaceutical Formulatioms. 2011; pp. 566-570.
3. Raghu B K. Eranki SR. S Sarma. GMJ Raju. GVS Sarma. EVS Subrahamanyam. and. V Sanjeeva kumar. Simple and Stability Indicating RP-HPLC Assay Method Developement and Validation for Enalapril Maleate by RP-HPLC in Bulk and Dosage Form. 2015; pp. 767-773.
4. Blenheim Pharmacal, Inc.
5. Horria M. Pakinaz Kh. and. Reem Sh. Spectrophotometric Determination of Some Angiotensin Converting Enzyme Inhibitors By Potassium Dichromate and Potassium Permanganate in Tablet Dosage Form. Asian Journal 27-12-2014; pp. 16-24.
6. Nafisur R. Sk Haque. Optimized and Validated Spectrophotometric Method for the Determination of Enalapril Maleate in Commercial Dosage Forms. 2008; pp. 32-43.
7. Abdel Fattah W. Saeid B. Eman. and. H. Ali K. Simultaneous Determination of Enalapril Maleate and Hydrochlorothiazide by First-Derivative Ultraviolet Spectrophotometry and High-Performance Liquid Chromatography. Journal of Pharmaceutical and Biomedical Analysis. 1995; pp. 851–856.
8. Abdullah M. Subrata B. Afroza H. Elias M. and. Syed H. Development and Validation of HPLC Method for Simultaneous Determination of Gliclazide and Enalapril Maleate in Tablet Dosage Form. Journal of Pharmaceutical Sciences. 2014.
9. Idress M. Determination of Hydrochlorothiazide and Enalapril Maleate in Tablet Formulations by Reversed-PhaseHPLC. Chemistry Department, Yarmouk University, Irbid-JORDAN. 2001; pp. 49 -54.
10. Xue-Zhi Q. Dominic P. Eric W. and. T sai. Determination and Rotamer Separation of Enalapril Maleate by Capillary Electrophoresis. Elsevier. 1992; pp. 251–258.
11. Mohammed H. Mohamed A E. Dina Sh. Dalia W. and. Saadia A. Simultaneous Determination of Enalapril and Hydrochlorothiazide in Pharmaceutical Preparations Using Microemulsion Liquid Chromatography. Journal of Chromatographic Science. 2014; pp. 90-96.
12. Qi G. Xiaoyan Ch. Dafang Zh. And. Yingwu W. Simultaneous Determination of Enalapril and Enalaprilat in Human Plasma by Liquid Chromatography–Tandem Mass Spectrometry. Elsevier. 2004; pp. 337–342.
13. Camila V. Eduardo D. Guilherme M. Luiz H. Dall A. César T. and. Elen S. An Improved Method for Simultaneous Square-Wave Voltammetric Determination of AmLodipine and Enalapril at Multi-Walled Carbon Nanotubes Paste Electrode Based on Effect of Cationic Surfactant. Elsevier. 2014.
14. Bruna L. Roberta M. and. Orlando F. Simultaneous Determination of Antihypertensive Drugs by Flow Injection Analysis Using Multiple Pulse Amperometric Detection With a Cathodically Pretreated Boron-Doped Diamond Electrode. Journal of Electroanalytical Chemistry. 2015; pp. 154–159.
15. Magda A. Abdalla Sh. Hisham A. and. Mervat H. Spectrophotometric and AAS Determination of Ramipril and Enalapril Through Ternary Complex Formation. Elsevier Science. 2002; pp. 311–321.
16. Shi Sh. Xing Y. and. Yaqin Sh. Application of Quantitative NMR for Purity Determination of Standard ACE Inhibitors. Journal of Pharmaceutical and Biomedical Analysis. 2015; pp. 190–199.
17. Seyyed A. Hassan T. Majid A. and. Mohammad S. Simultaneous .Determination of Hydrochlorothiazide and Enalapril Maleate in Pharmaceutical Formulations Using Fourier Transform Infrared Spectrometry. 2011; pp. 59-67.
18. G.D Chrestian. P.K Dosguspts. and. K. A Schug. Analytical chemistry. 6th edition. 2004.
19. United State Pharmacopeia 24. 2000.
Received on 07.10.2017 Modified on 17.11.2017
Accepted on 24.12.2017 © RJPT All right reserved
Research J. Pharm. and Tech 2018; 11(2):723-729.
DOI: 10.5958/0974-360X.2018.00136.1