INTRODUCTION:

Aripiprazole is chemically a quinolinone derivative used as an anti-psychotic and anti depressant drug for treatment of schizophrenia and schizoaffective disorders¹. It has potent partial agonist activity at dopamine 2 receptors, partial agonist activity at serotonin A receptors and antagonist activity at 5HTZA receptors^2-3. Knowledge of pharamacokinetics of a Aripiprazole in patients suffering from schizophrenia is limited.

Aripiprazole, chemically 7-[4-[4-(2, 3-dichlorophenyl) piperazin -1- yl] butoxy] - 3, 4-dihydro-1H-quinolin-2-one, is an anti-psychotic agent having its empirical formula as C₂₃H₂₇Cl₂N₃O₂ and its molecular weight is 448.38. Its structure is given below.

Literature survey reveals a few HPLC methods,one HPTLC method, one LC- MS/MS method,one capillary electrophoresis method, and some UV as well visible methods have been developed for estimation of aripiprazole in human serum, tablet and pure form.^4-12

EXPERIMENT:

Objective:

The objective of the present investigation is to develop simple, accurate and economical visible spectrophotometric methods for quantitation of aripiprazole in bulk formulation.

MATERIALS AND METHODS:

Instrumentation: Elico SL 177 Visible Spectrophotometer wavelength accuracy of ± 0.3 nm and 1.0 cm matched quartz cells was used for analytical method development.

Preparation of stock solution and experimental solution:

Standard solution of Aripiprazole(ARP) was prepared by dissolving 50 mg in 50 ml of ethanol and diluting 10 mL of this solution to 100 mL with ethanol (100μg/mL). 50 mg of pure Aripiprazole is transferred into a 50 mL volumetric flask containing 20 mL of ethanol and flask was kept for ultrasonication for 3 min, then it is diluted up to the mark with ethanol solution. From the above solution 5ml and 10 mL are pipetted out into a 100 mL volumetric flask separately and the volumes are made up to the mark with ethanol. These final concentrations of Aripiprazole are used for the analysis of method 1 and method2 respectively.

Method I^13-14: In the first method aliquots of Aripiprazole ranging from 0.5-5 mL of standard solution of 100ppm are transferred to each 25 mL calibrated tubes, 0.5 mL of 5% w/v acetic acid and 2ml of 0.1% N-Bromosuccinimide (NBS) standardized iodometrically solutions were added to the above solutions and volume in each tube was brought to 10ml with double distilled water and kept aside for 20minutes at room temperature. Then 2ml of 0.3% metol (p-N-methyl aminophenol sulphate) solution was added. After 2minutes, 2ml of 0.2% sulphanilamide(SA) solution was added and volume was made upto the mark with double distilled water. The absorbance’s are measured after 10minutes at 520nm against double distilled water. A blank experiment was also carried out by omitting the drug. The decrease in absorbance and in turn the drug concentration was obtained by subtracting the absorbance of the test solution from the blank. The calibration graph was drawn by plotting the decrease in the absorbance.

The proposed reaction for the method-I is

NBS (unreacted) + PMAP (metol)→2PMBQMI

PMBQMI +SA→ charge transfer complex

Method II^13-14:

In the second method aliquots of Aripiprazole ranging from 0.1ml- 0.4mL of 50 ppm standard solution is transferred in to a series of graduated tubes, 1.25ml of 5M HCl and 2.0ml of 0.02% Chloramine-T(CAT) standardized iodometrically were added and the solution was diluted to 20ml with double distilled water. After 10minutes, 5ml of 0.01% Gallocyanine(GC) was added, mixed thoroughly and the absorbance’s are measured after 15minutes at 540nm against double distilled water. A blank experiment was also carried out in a similar manner. The decrease in absorbance corresponding to consumed chloramines-T, which in turn the drug concentration was obtained by subtracting the absorbance of the blank solution from that of the test solution. The calibration graph was drawn by plotting the decrease in the absorbance of the dye against amount of the drug.

The proposed reaction for the method-II is

(ARP)Drug + CAT (excess) → Oxidation products of drug + un reacted CAT

CAT (unreacted) + → unreacted dye + mixture of compounds

with conjugation

Recovery Studies:

The recovery was in the range: 99-100 % for Method-1 and 98-100 % for Method-2.

RESULTS AND DISCUSSION:

The proposed methods are in accordance with Beer’s law in the concentration range of 1-20 µg/ml for N-Bromosuccinimide and Chloramine-T 0.2-0.8µg/ml. The recovery studies were carried out by standard addition method and were found close to 100 %.

For the methods developed the following parameters were validated and tabulated in the Table1 below. Hence the above developed methods may be used for the routine estimation of aripiprazole in bulk formulation.

VALIDATION RESULTS

Table1: Optical Characteristics of Aripiprazole

PARAMETERS	METHOD I	METHOD II
λ max	520.0 nm	540.0 nm
Beer’s law limit (µg/ml)	1-20 µg/ml	0.2-0.8 µg/ml
Regression equation^* (y = a + bc )	y = 0.0362x + 0.0084c	y = 1.0263x + 0.0058c
Slope ( b)	0.0362	1.0263
Intercept ( a)	0.0084	0.0058
Correlation coefficient (r²)	0.9994	0.9994
Molar Absorptivity	1.65X10⁴	4.6X10⁴
Sandell’s Senstivity (g/cm²/ 0.001 abs unit)	1.135 X 10^-4	1.852 X 10^-2

* y = a + bc, where c is the concentration in µg/ml, y is the absorbance unit of four replicate samples and b is the slope of line equation.

Spectral Characteristics of Aripiprazole

GRAPHS

REFERENCES:

1. Seftel AD. Phosphodiesterase type 5 inhibitor differentiation based on selectivity, pharmacokinetic, and efficacy profile. Clin Cardiol. 2004;27(4 suppl 1):I14-I19.

2. Merck index, 13th ed., Merck. In. Co., NJ-USA: 2001, p. 134

3. Aripiprazole., Wikipedia, the fre Encyclopedia

4. J.K.McGavin ,K.L. Goa ,.Ingenta connect., 2002, 16, 11, 779

5. R. Kalaichelvi, B.Thangabalan, D. Srinivasarao and E. Jayachandran, E-Journal of Chemistry 2009., 6(S1), S87-S90

6. Akamine Y, Yasui-Furukori N, Kojima M, Inoue Y, Uno T; sensitive column-switching HPLC method for aripiprazole and dehydroaripiprazole and its application to human pharmacokinetic studies.

7. Anthony de Leon., Nick, C.Patel.,Lynn Crimson,M.,Clinical Therapeutics., 2004, 26,5.

8. Suresh Mallikararjun, Daniel, E.Salazar and Steven.L., Journal of Clinical Pharmacology., 2004, 44, 179-187

9. Shailesh, S.Vengurlekhar., Simultaneous LC-MS/MS Determination of Aripiprazole (OPC-14597) and its five major metabolites in Human Urine

10. Musenga A and Saracino M A., Anal chim Acta., Vol. 612, issue 2, pg.204-21, 2008.

11. Vijaya kumar.M and Muley., The Indian Pharmacist., 2005, April, 71

12. Attri N., Yadav S and Goyal A., www.scientificipca.org /paper/2009/09/13/200909131216450A.doc

13. Becket A H and Stenlake J B, Practical Pharmaceutical Chemistry, 4th Edition; CBSPublishers and distributors, New Delhi, Part 2, 304.

14. Green J M, A Practical guide to analytical method validation, Anal Chem., News Feat 305A/309A, 1996, May 1.

Received on 23.09.2011 Modified on 18.10.2011

Asian J. Research Chem. 4(11): Nov., 2011; Page 1752-1754