INTRODUCTION:

Quetiapine fumarate is an psychotropic agent^1,2, the dibenzo thiazepine derivative and it is chemically³ 2-[2-(4-dibenzo [b,f] [1,4] thiazepin-11yl-1 piperazinyl) ethoxy]-ethanol fumarate. Literature survey revealed only few chromatographic methods^4-7for the estimation of Quetiapine fumarate in plasma of human and with other antipsychotic drugs in human blood⁸ Literature survey did not reveal any spectrophotometric method for estimation of Quetiapine fumarate in bulk drug and dosage form. The objective of this investigation is to develop a simple, accurate and reproducible visible spectroscopic method.

EXPERIMENTAL:

Instrument:

Perkin Elmer EZ301-Double beam spectrophotometer

Reagents:

1) Standard stock solution (1mg/ml) A stock solution of drug was prepared by dissolving accurately weighed 50mg of Quetiapine fumarate in 50ml distilled water.

2) Chloroform AR

3) 0.1% W/V Bromocresol green solution and phthalate buffer of pH 2.8 were prepared as per I.P ⁹.

Procedure:

Preparation of calibration curve:

5ml of standard stock solution was diluted to produce 100mcg/ml (Stock solution II). Aliquouts of 0.5ml-2.5ml of stock solution II were taken in five separating funnels followed by addition of 2ml dye solution (0.1%) and 2ml buffer (pH 2.8) and volume was made up to 10ml with distilled water. The aqueous layer was extracted three times with chloroform. The combined chloroform extract was collected and diluted to 10ml to produce concentration in the range of 5-25 mcg/ml. Absorbance of each resulting solution was measured at 415nm against reagent blank and absorbance was plotted versus concentration to get the calibration curve. (Fig 1).

Preparation of sample:

Twenty tablets were weighed and average weight was determined. An accurately weighed tablet powder equivalent to 25mg of Quetiapine fumarate was transferred into 25ml volumetric flask, dissolved with little distilled water and then volume was made up to the mark with distilled water. This aqueous solution was then filtered using whatmann filter paper (Grade-I). 5ml of this filtrate was suitably diluted with water to get 100mcg/ml (Stock solution II). 1ml of this solution was transferred into a separating funnel followed by the addition of 2ml buffer(pH2.8), 2ml dye solution (0.1%) and volume was made up to 10ml with distilled water. The aqueous layer was extracted with chloroform and combined chloroform extract was collected and made up to 10ml with chloroform. The same procedure was repeated with the standard solution of drug at the same concentration (10mcg/ml). The absorbance of each resulting solution was measured at 415nm against reagent blank.

Table 1. Optical characteristics and precision

Parameters	Proposed method
λmax	415nm
Beer’s law range(mcg/ml)	5-25
Sandell’s sensitivity (µg/cm²/0.001 absorbance unit)	0.01949
Molar absorptivity(mole^-1cm^-1)	4.5x10⁴
LOD(mcg/ml)	0.29
LOQ(mcg/ml)	0.88
Stability	90 mts
Regression equation(Y^*) Slope Intercept Correlation coefficient	0.0513 0.0013 0.9999

Y^*= b+aC; where ‘C’ is concentration in mcg/ml and Y is absorbance unit.

Table 2 : Results of analysis in marketed formulations

Formulations

Parameters

%Labelled claim^*

%Recovery^*

SOCALM

Mean

±SD

%RSD

97.44

0.32

1.29

98.83

0.27

QUTIPIN

Mean

±SD

%RSD

96.68

0.078

0.32

98.98

0.35

* Mean of five determinations SD-Standard deviation, RSD-Relative standard deviation.

RESULTS AND DISCUSSION:

The λmax of Quetiapine fumarate was found to be 415nm from its spectrum. It showed linearity in the concentration range of 5-25 mcg/ml. The molar absorptivity is 4.5x10⁴(mole^-1cm^-1) and sandell’s sensitivity was 0.01949 (µg/cm²/0.001 absorbance unit).The correlation coefficient (r) was found to be 0.9999. The LOD and LOQ values were determined from the slope of linearity plot and standard deviation of Y-intercept and found to be 0.29 and 0.88 mcg/ml respectively. The stability of colour of resulting solution was determined by measuring the absorbance at 415nm at 15mts time intervals. There was no considerable change in the absorbance at this wavelength upto 90 minutes. Commercial formulations containing Quetiapine fumarate were analyzed by proposed method. Five replicate analysis of the formulation were carried out and mean assay values in tablet formulation SOCALM and QUTIPIN were found to be 97.44±0.3286 and 96.68±0.07854. The corresponding RSD values were found to be 1.29% and 0.32% indicating that the method has required precision. The accuracy of the method was determined by recovery studies. Pure Quetiapine fumarate was added (5mg) to the preanalysed tablet powder and the mean recovery of Quetiapine fumarate was found to be 98.83±0.2738 and 98.98±0.3535 indicating that the method has required accuracy. The validation results were given in table 1 and 2.

CALIBRATION CURVE OF QUETIAPINE FUMARATE

CONCLUSION:-

Thus, the developed method is simple, accurate, precise, reproducible, less time consuming and effective. Hence, it can be used for routine analysis of Quetiapine fumarate in bulk and pharmaceutical formulations.

ACKNOWLEDGEMENTS:-

The authors extend their sincere thanks to Torrent pharmaceuticals, Ahmedabad for providing gift sample of pure Quetiapine fumarate. We also extend our thanks to Chairman, K.M College of pharmacy, Madurai -107, for providing the necessary facilities.

REFERENCES:-

1. Richelson E. Receptor pharmacology of neuroleptics: relation to clinical effect. J. Clin. Psychiatry. 1999; 60(10): 5-14.

2. Arvanitis L.A., Miller B.G. Multiple fixed doses of “seroquel” in patients with acute exacerbation of schizo-phrenia: a comparison with haloperidol and placebo. Biol. Psychiatry. 1997;42: 223-226.

3. Remington pharmaceutical science. 21^st ed, Vol.2. 1437.

4. Barrett B., Holcapek.M., Hucloca.J., Borek.V., et al., Validated HPLC-MS/ms method for determination of Quetiapine in human plasma. J. Pharm. Biomed. Anal. 2007; 44(2):405-408.

5. Hasselstom J., Linnet K. Fully automated on-line quantification of Quetiapine in human serum by solid phase extraction and liquid chromatography. J. Chromatograph. Biomed. Anal. 2003; 798(1): 9-19.

6. Saracino M.A., Mercolini L., Fiotta G., Albers L.J., et al., Simultaneous determination of fluvoxamine isomers and Quetiapine in human plasma by HPLC. J. Chromatograph. Biomed. Anal. 2006; 843(2): 227-233.

7. Berlin S., Heidelebrg. Simultaneous analysis of classical neuroleptics, atypical antipsychotic and their metabolites in human plasma. J. Anal. Bioanal. Chem. 2007; 388(1): 235-243.

8. Sachse J., Koller J., Harther S., Christopher. Automated analysis of Quetiapine and other antipsychotic drugs in human blood by HPLC with column switching and spectrophotometric detection. J.Chromatograph. Bioanal.Chem. 2006; 830(2):342-348.

9. Indian Pharmacopoeia, Vol. 2 (1996) A-144.

Received on 01.07.2009 Modified on 29.08.2009

Research J. Pharm. and Tech.2 (4): Oct.-Dec. 2009; Page 880-881