*Corresponding Author:
I. Singhvi
Sanjeevan College of Pharmacy, Dausa-303 303, India
E-mail:
[email protected]
Date of Submission 08 August 2006
Date of Revision 14 July 2008
Date of Acceptance January, 2009
Indian J Pharm Sci, 2009, 71 (1): 66-68  

Abstract

Two simple and sensitive visible spectrophotometric methods have been developed for the quantitative estimation of ketotifen fumarate from its tablet formulation. The developed methods are based on formation of chloroform extractable colored complex of with 2-nitroso- napthol-4- sulphonic acid and rhodizonic acid. The extracted complex of drug with 2-nitroso- napthol-4- sulphonic acid (method-I), showed absorbance maxima at 436.5 nm and with rhodizonic acid (method-II), showed absorbance maxima at 489.5 nm. The linearity range for both the developed methods was observed in the concentration range of 50-250 µg/ml of drug. Results of analysis for both the developed methods were validated statistically and by recovery studies.

Keywords

Spectrophotometric, ketotifen fumarate, 2-nitroso- napthol-4-sulphonic acid and rhodizonic acid

Ketotifen fumarate, 4,9-dihydro-4-(1-methyl-4- piperidinylidene)-10-H-benzo[4,5] cycloheptal- [1,2-b] thiophen-10-one fumarate, is used as an antiasthamatic agent [1]. Few analytical methods for estimation of ketotifen fumarate including GC [2,3], HPLC [4-6] and spectrophotmetric [7-9] are reported.

A Jasco UV/Vis double beam spectrophotometer (model 7800) with 1 cm matched quartz cells was used for spectral measurement. All the chemical used were of analytical grade, a 1% solution of 2-nitrosonapthol- 4-sulphonic acid (Thomas Baker, Mumbai, India) and 2% solution of rhodizonic acid (Thomas Baker, Mumbai, India) were prepared in distilled water and extracted several times with chloroform so as to remove chloroform soluble impurities. Standard drug solution of ketotifen fumarate (500 μg/ml) was prepared in distilled water. The tablet sample of ketotifen fumarate was procured from the local pharmacy.

In a series of 10 ml volumetric flasks aliquots of standard drug solution of ketotifen fumarate in distilled water were transferred and diluted with the same so as to give several dilutions in the concentration range of 50-250 μg/ml of drug. For the method I, to each dilution (5 ml) taken in a separating funnel, 5 ml of 2-nitroso-napthol- 4-sulphonic acid solution was added and shaken for 10 min for the formation of colored complex. The colored complex was extracted with 5, 3, and 2 ml portions of chloroform, the volume of combined chloroform layer was made up to 10 ml and absorbance was measured at 436.5 nm against a reagent blank. A calibration curve was prepared by plotting concentration versus absorbance.

For the method II, to each dilution (5 ml) taken in a separating funnel, 5 ml of rhodizonic acid solution was added, shaken and allowed to stand for 10 min for the formation of colored complex. The colored complex was extracted with 5, 3, and 2 ml portions of chloroform, the volume of combined chloroform layer was made up to 10 ml and absorbance was measured at 489.5 nm against a reagent blank. A calibration curve was prepared by plotting concentration versus absorbance.

For analysis of formulation, twenty tablets of ketotifen fumarate were accurately weighed and average weight per tablet was determined. The tablets were powdered and powder equivalent to 10 mg of ketotifen fumarate was accurately weighed and extracted four times with 20 ml portions of distilled water, the combined extract was filtered through Whatman filter paper No. 41 in to 100 ml volumetric flask. The residue was washed with distilled water and the washing was added to the filtrate, final volume of filtrate was made up to the mark with distilled water. Filtrate (10 ml) was treated as per the respective procedure for the calibration curve and absorbance was measured at 436.5 nm (method-I) and 489.5 nm (method-II), the amount of drug present in sample was computed from respective calibration curve.

Analysis for both the developed methods was repeated five times for three different batches of tablet formulations. Results of analysis are reported in Table 1. Recovery studies were carried out for both the developed methods by addition of known quantity of pure drug solution to pre analyzed tablet sample solution at three different concentration level. The result of recovery studies is reported in Table 1.

Method Formulation Label Claim
mg/tab
% of label claim estimated* Standard deviation % Recovery** Standard deviation
I
NitrsoNapthol
Tablet I 01 99.63 0.685 99.06   0.653
  Tablet II 01 98.78 0.794 99.65 0.893
II
Rhodizonic acid
Tablet III 01 99.01 0.589 98.98 0.624
   Tablet I 01 98.1 0.508 100.70 0.543
  Tablet II 01 98.9 0.789 99.54 0.872
  Tablet III 01 99 0.812 99.84 0.842

Table 1: Analysis of Tablet Formulation

The proposed spectrophotometric methods for determination of ketotifen fumarate from tablet formulations are based on formation of chloroform extractable colored complex of drug with 2-nitrosonapthol- 4-sulphonic acid and rhodizonic acid. The results of analysis for both the developed methods were close to 100% and standard deviation was satisfactorily low indicating accuracy and reproducibility of the methods. Recovery studies were satisfactory which shows that there is no interference of excipients. The developed methods were found to be simple, rapid, accurate and can be used for routine analysis of drug from tablet formulations.

References

  1. Budavari S. The Merck Index. 12th ed. Whitehouse Station, NJ: Merck and Co. Inc; 1996. p. 836.
  2. Xiaoyan C, Dafang Z, Dan L, Yingwu W, Ying H, JingkaiG.Determination of ketotifen and its conjugated metabolite in human plasma by mass spectrometry application to a pharmacokinetic study. Rapid CommMass Spectrom 2003;17:2459-63.
  3. Florey K. Analytical Profile of Drug Substance. London: Academic Press; 2005. p. 258.
  4. Naomi Y, Yoshikuni T, Keinosuke H, Jun-ichi S, Hitoshi S. Pharmacokinetics of ketotifenfumarate after intravenous, intranasal, oral and rectal administration in rabbits. Biol Pharm Bull 2002;25:1614-8.
  5. Nane P, Damani LA, Hutt AJ. Development and validation of stability indicating high-performance liquid chromatographic assays for ketotifenin aqueous and silicon oil formulations. Chromatographia 1998;48: 797-802.
  6. Elsayed M. Development and validation of a rapid HPLC method for the determination of ketotifen in pharmaceuticals. Drug Develop Ind Pharm 2006;32:457-61.
  7. Sastry CSP, Naidu PY, Murty SSN. Visible spectrophotometric methods for the determination of ketotifenfumarate. Eastern Pharmacist 1997;40:133-5.
  8. Chilukuri SP, Petla YN. Spectrophotometric estimation of ketotifenfumarate in pharmaceutical formulations. MicrochimicaActa 1997;127:219-23
  9. Sastry CS, Naidu PY, Murty SS. Three simple spectrophotometric methods for the assay of ketotifenin pharmaceutical formulations. Indian J Pharm Sci 1997;59:93-5.