INTRODUCTION:

Quetiapine fumarate is an psychtropic 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 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.

EXPERIMENTAL:

Materials and Equipment:

Pure drug was obtained from Torrent pharmaceuticals, Ahmedabad as a gift sample. SOCALM and QUTIPIN were tablet formulation purchased from the market. Distilled water was used as solvent for entire experiment. Perkin Elmer EZ301, a double beam UV-Spectrophotometer with 1cm matched Quartz cells were used for the measurement of absorbance. Dhona 1600-Analytical single pan balance was used for weighing the samples.

Procedure:

Preparation of standard solution:

Quetiapine fumarate standard stock solution (1mg/ml) was prepared in distilled water. From this stock solution, working standard solution (10mcg/ml) was prepared by appropriate dilution with distilled water.

Determination of λmax and A(1%,1cm) value

Working standard solution of Quetiapine fumarate was scanned in the entire uv range of 200-400nm. The λmax and A(1%,1cm) of Quetiapine fumarate were found to be 290nm(Fig No 1) and 186.22 ± 3.11 respectively.

Preparation of calibration curve:

Standard stock solution prepared in distilled water was diluted suitably with distilled water to obtain concentrations ranging from 5-25 mcg/ml. Absorbance of resulting solutions was measured at 290nm. Absorbance was plotted versus concentration to obtain the calibration curve (Fig No 2)

From the calibration curve, the linearity range was found out and LOD and LOQ values were calculated using the relation,

LOD=3.3 σ/S

LOQ=10 σ/S

Where σ = standard deviation of residuals from the curve; S = slope of the curve

Analysis of the marketed formulation:

Twenty tablets were weighed and its 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 made up to the mark. This aqueous solution was then filtered using whatmann filter paper (Grade-I). 5ml of this filtrate was then taken and suitably diluted with distilled water to obtain 10mcg/ml solution. The absorbance of this solution was compared to the absorbance of 10mcg/ml standard solution to estimate the Quetiapine fumarate content in the tablets. Results of assay were shown in Table 1.

Table 1:- Results of Analysis in marketed formulation

Drugs

Parameters

%Labelled claim*

%Recovery*

SOCALM

Mean

± SD

%RSD

100.64

0.18

0.72

102

1.14

1.11

QUTIPIN

Mean

± SD

%RSD

101.32

0.35

1.4

98.8

1.10

1.12

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

Fig No 1 Spectrum of Quetiapine Fumarate

Recovery studies:

To determine the accuracy of the method, recovery study was performed by standard addition method. To the preanalysed tablet powder equivalent to 25mg (labeled claim of a tablet), known quantity of standard drug (5mg) was added and total drug contents were described as for formulation. The % recovery was determined and the results were given in table No:1.

RESULTS AND DISCUSSION:

The λmax of Quetiapine fumarate was found to be 290nm from its spectrum. The A(1%, 1cm) value was found to be 186.22 ± 3.11. Quetiapine fumarate showed linear absorption from 5-25 mcg/ml. The correlation coefficient (r) was found to be 0.9997. The LOD and LOQ values were determined from the slope of linearity plot and standard deviation of Y-intercept and found to be 0.41mcg/ml and 1.25mcg/ml respectively. The stability of solutions of formulation was determined by measuring the absorbance at 290nm at periodic intervals. There was no considerable change in the absorbance at this wavelength up to 3hrs.

Commercial formulations containing Quetiapine fumarate were analysed by proposed method. Five replicate analysis of the formulation were carried out and the mean assay values in tablet formulation SOCALM and QUTIPIN were found to be 100.64 ± 0.18 and 101.32 ± 0.35. The corresponding RSD values were found to be 0.72% and 1.4% 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 102 ± 1.14 and 98.8 ± 1.10 % indicating that the method has required accuracy. The validation results were given in Table 1.

Fig No 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 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. Chrmatograph. 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.Chrmatograph.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.

Received on 25.07.2009 Modified on 30.09.2009

Asian J. Research Chem. 2(4):Oct.-Dec. 2009 page 452-453