Introduction

Quetiapine fumarate (QTF), 2-[2-(4-(Dibenzo [b, f] [1, 4] thiazepin-11-yl-1-piperazenyl] ethoxy) ethanol] fumarate) is a dibenzothiazepine derivative and used as antipsychotic drug1. Cilostazol (CLZ), 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxyl]-3, 4-dihyro-2(1H)-quinolinone is a phosphodiestrase inhibitor with antiplatelet and vasodilating activity1.

Literature survey revealed spectrophotometric2 and HPLC3 – 5 methods for estimation of QTF in bulk, formulations and biological fluids. Few chromatographic methods6 – 9 have been reported for estimation of CLZ in bulk, formulation and biological fluids. Both these drugs are not official in IP, BP and USP.  Therefore, an attempt has been made to develop simple UV-Spectrophotometric method and validate it for accuracy, precision and ruggedness10.

Material and Methods

All the measurement were made using UV- visible spectrophotometer (Shimadzu-2450 with UV probe 2.21 software), with 10 mm quartz cell and spectral bandwidth 1nm.

Chemicals used were of analytical grade

Preparation of standard stock solutions QTF and CLZ

Accurately weighed 10 mg of QTF was dissolved in 100 ml of double R.O water to obtain 100 ug/ml of working standard solution. Stock solution 100 ug/ml for CLZ was prepared by dissolving 10 mg of CLZ in 100 ml of acetonitrile (30% v/v). Different aliquots were taken from the stock solutions, diluted to 10 ml mark with respective solvents to obtain series of concentrations. Absorbances were measured at 290 nm for QTF and 258 nm for CLZ against blank. The calibration curve was linear in the concentration range 6-54 µg/ml (Y = 0.0187 X + 0.0044; r2= 0.9999) for QTF and 3 – 21 µg/ml (Y = 0.04525 X + 0.0055; r2 = 0.9993) for CLZ.

Preparation of Sample Solution

An accurately weighed amount of tablet powder (QTF) equivalent to 10 mg was dissolved in 100 ml of double R.O. water, sonicated for 15 min and filtered through Whatmann filter paper no.41. After appropriate dilutions, absorbance of sample was recorded at 290 nm and concentration was determined by linear regression equation.

An accurately weighed amount of tablet powder (CLZ) equivalent to 10 mg was dissolved in 100 ml of acetonitrile (30% v/v), sonicated for 15 min and filtered through Whatmann filter paper no 41.After appropriate dilutions, absorbance of sample  was measured at 258 nm and concentration was determined by linear regression equation.

Table 1: Results of assay.

* mean of five estimations

The results of analysis for QTF and CLZ are shown in Table 2.

Table 2: Summary of validation.

* mean of three estimation at each leve

Recovery studies

To study the accuracy of the proposed method, recovery experiments were carried out by adding a known amount of standard drug solution to preanalysed sample solution at three different levels i.e. 80%, 100% and 120% and re-analysed the samples using proposed method. The results are shown in Table 2.

Results and Discussion

QTF in double R.O. showed lmax at 290 nm. CLZ in acetonitrile (30% v/v) showed lmax at 258 nm. QTF and CLZ follows linearity in the concentration range 6 – 54 µg/ml and 3 – 21 µg/ml at respective wavelengths. The analysis of tablet formulation by proposed methods was in good agreement with the label claimed. The methods were validated for accuracy, precision and ruggedness. The low values of %RSD indicate method is accurate and precise. Ruggedness of the proposed methods was studied with the help of two analysts and proven to be rugged. The results from validation studies are shown in Table 2. The proposed methods are simple, rapid, accurate, economical and used for the routine analysis of QTF and CLZ from marketed formulations.

References

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3. Kumar V.M., Muley P.R., “Stability indicating HPLC method for determination of quetiapine fumarate in bulk and solid dosage forms.” Ind. Drug, 41: 272 (2004).
4. Davis P.C., Wong J., Gefvert O., “Analysis and Pharmacokinetics of Quetiapine and two metabolites in human plasma using reversed phase HPLC with ultraviolet and electrochemical detection.” J. Pharm. Biomed. Anal., 20: 271-/282. (1999).
5. Raggi M.A., Fanali S., Mandrioli R., Bugamelli F., Volterra V., “HPLC analysis of the novel antipsychotic drug quetiapine in human plasma.” J. Pharm.Biomed. Anal. 30: 969-/977 (2002).
6. Prasad N. V. Tata, Chau Hwei J. Fu, Steven L. Bramer. “Determination of cilostazol and its metabolites in human urine by high performance chromatography.” J. Pharm. Biomed. Anal., 24: 381-389 (2001).
7. Steven L. Bramer, Prasad N. V. Tata, Shailesh S. Vengurlekar and Jerry H. Brisson. “Method for the quantitative analysis of cilostazol and its metabolites in human plasma using LC/MS/MS. “ J. Pharma. Biomed. Anal., 26:
   637-650 (2001).
8. ChauHwei J. Fu, Prasad N. V. Tata, Keizo Okada, Hitoshi Akiyama and Steven L. Bramer. “Simultaneous quantitative determination of cilostazol and its metabolites in human plasma by high-performance liquid chromatography.” J. Pharm. Biomed. Anal., 728: 251-262 (1999).
9. Akiyama, H., Kudo, S., Odomi, M. and Shimizu, T. “High-performance liquid chromatographic procedure for the determination of a new antithrombotic and vasodilating agent, cilostazol, in human plasma” J. Chromatogr.Biomed. Appl. 338:  456–458 (1985).
10. United State Pharmacopeia, 28thedn. United State Pharmacopoeial Convention. Inc., Rockville, 2749 (2005).