International Journal of Drug Development and Research

Key words

Aliskiren, Amlodipine, Q-analysis, Simultaneous equation.

INTRODUCTION

Analytical chemistry1 may be derived as the science and art of determining the composition of material in terms of the elements of compounds contained. In instrumental analysis, a physical property of the substance is measured to determine its chemical composition. Analysis of minute amounts of complex biological materials to the quality control of the final dosage form, the use of analytical technology covers an immense range of techniques and disciplines. The qualitative and quantitative analysis2 can be done by various analytical methods. Modern analytical techniques employ a range of techniques that vary from simple qualitative chemical test to the use of most sophisticated and expensive computer controlled instruments. Analytical instrumentation plays an important role in the production and evaluation of products. Analytical method is a specific application of a technique to solve an analytical problem.

Aliskiren (2(S), 4(S), 5(S), 7(S)- N-(2-carbamoyl-2- methylpropyl)- 5-amino-4-hydroxy-2,7-diisopropyl - 8-[4-methoxy-3-(3-methoxypropoxy)phenyl]- octanamide hemifumarate) is an orally active renin inhibitor licensed for the treatment of essential hypertension. It is more expensive than most other antihypertensive agents and no long term clinical outcome data are available. Aliskiren metabolized slowly in the body resulting in stronger half lives which restrict it once a day dosing. The cytochrome P450 susceptibility is also less and a major proportion of the drug is eliminated unchanged via feces.

Amlodipine ((RS)-3-ethyl 5-methyl 2-[(2- aminoethoxy) methyl]-4-(2-chlorophenyl)-6- methyl- 1, 4-dihydropyridine-3,5-dicarboxylate ) is long acting calcium channel blockers used as an antihypertensive and in the treatment of angina. It acts by relaxing the smooth muscle in the atrial wall, decreasing total peripheral resistance and hence reducing blood pressure, in angina it increases blood flow to the heart muscle. Various analytical methods have been reported for the assay of Amlodipine3 in pure form as well as in pharmaceutical formulation. They include HPLC4, 5, HPTLC6, RP-HPLC7, 8, gas chromatography9, mass-spectrometry10, and flourimetry11.

MATERIALS AND METHODS

Chemicals and reagents

Spectral runs were made on a Jasco V-530 UVVisible spectrophotometer. Aliskiren and Amlodipine reference standard was kindly provided by Novartis Pharmaceuticals Ltd, India. All the reagent was purchased from Merck Pvt. Ltd.The solution were protected from light and were analyzed on the day of preparation.

Preparation of Standard Drug solution for Method I and II

Standard stock solution for Aliskiren and Amlodipine were prepared separately by dissolving 100mg of both drugs with methanol in 100ml volumetric flask i.e. 1000μg/ml. A 10ml solution was pipette out and the volume was made up to the mark with methanol i.e. 100 μg/ml each of Aliskiren and Amlodipine in two different 100ml volumetric flask.

Determination of Absorption Maxima for Method I and II

Standard stock solutions of Aliskiren and Amlodipine were scanned in the range of 200 – 400 nm against Methanol as a blank. Aliskiren and Amlodipine showed absorbance maxima at 279 nm and 361 nm respectively. The overlain spectra showed λmax of both drugs was recorded (isoabsorptive point) at 289 nm.

Method I (Q-Analysis)

The method involves the overlain spectrum of two drugs, two wavelengths were selected one is the isoabsorptive point for both the drugs and the other is λ1 or λ2 max of either of the two drugs. The stock solutions are prepared and the absorptivity values for both drugs at the selected wavelengths are calculated. The method employs Qo - values and the concentrations of drugs in sample solution were determined by using the following formulas,

For Aliskiren For Amlodipine

Where,

Method II (Simultaneous estimation)

The method involves selecting two wavelengths λ1 or λ2 for the simultaneous estimation of two drugs (A & B) are that are absorption maxima of the drugs. The stock solutions of both the drugs were measured at the selected wavelengths and absorptivity (A 1%, 1cm) for both the drugs at both the wavelengths were determined as mean of three independent determinations. Concentration in the sample were obtained by using following equations,

A1 and A2 are the absorbances of mixture at λ1 and λ2 respectively.

ax1 and ax2 are absorptivites of drug A at λ1 and λ2 respectively and ay1 and ay2 are absorptivites of drug B at λ1 and λ2 respectively.

CX and CY are concentrations of drug A and drug B respectively.

RESULTS AND DISCUSSION

VALIDATION

Linearity: Linearity was checked by preparing standard solution at different concentration of Aliskiren and Amlodipine. For Q-analysis and simultaneous equation range was found to be 20-100 μg/ml and 5-25 μg/ml.

Method Precision: The precision of the methods was checked by repeated measurement of the absorbance of standard solutions (n = 6) of 20 μg/ml without changing the parameters for the method. The repeatability was expressed in terms of Relative Standard Deviation (RSD).

Intermediate Precision: Intraday precision carried out by taking 3 different concentrations at various days and performed as per method and calculated mean absorbance and % RSD.

CONCLUSION

The three proposed methods to be linear, precise, accurate, simple, and selective and sensitive have been developed. The order of sensitivity is as follows M I>M II.When compare to M I and MII, M I is considered for simultaneous estimation by Qanalysis method, MII is considered for simultaneous estimation by equation method. The described methods give accurate and precise results and can be used for simultaneous analysis of Aliskiren and Amlodipine.

Conflict of Interest

NIL

Source of Support

NONE

ACKNOWLEDGEMENTS

The authors are thankful to the management of Srinivas college of Pharmacy for providing necessary facilities and Novartis Pvt.Ltd. for providing Aliskiren and Amlodipine.

Tables at a glance

Table 1 Table 2 Table 3 Table 4 Table 5

References

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