Spectrophotometric determination of cabergoline in tablet dosage forms.

 

C. Rambabu¹, Dr. C.A. Jyothirmayee², K. Naga Raju^3*

¹Professor, Department of Chemistry, A. N. U. PG Centre Nuzvid-521201,

²Reader and head, Department of Chemistry, St. Theresa’s College for Women, Eluru-534003,

ABSTRACT:

New, simple, selective and accurate spectrophotometric methods are described in the present work for the determination of cabergoline in the pure samples and pharmaceutical formulations. Both the methods are based on the ion association complex formation of cabergoline with alizarin red S(ARS) and naphthol blue black(NBB) to form yellow and purple colored chromogen with absorption maxima at 425nm and 585nm respectively.  Beer's law is obeyed in the concentration ranges of 1-6 µg/ml and 2-12 µg/ml respectively.  The results of analysis for the two methods have been validated statistically and by recovery studies. The methods are extended to pharmaceutical formulations

 

1. INTRODUCTION:

Cabergoline¹1-[(6 allyergoline 8b -yl)]-carbonyl]-1-[3(dimethyl imino)propyl] - 3 ethyl urea is a dopamine agonist licensed for the treatment of Parkinson’s disease as adjunctive treatment with levodopa plus a dopa- decarboxylase inhibitor in patients effected by    on-off mobility problems. Cabergoline is a selective, ergoline, dopamine D2 agonist.           

 

Previous literature reveals that few analytical ^{1, 2} and biological ^3-7 methods have been reported for its quantitive estimation.  In the present work, two simple, selective and accurate visible spectrophotometric methods have been developed for the quantitative estimation of cabergoline.

 

In these methods the presence of tertiary nitrogen group in cabergoline enabled the use of ion association complex formation reaction with the acid dyes like alizarin red S and naphthol blue black to form yellow and purple colored chromogen with absorption maxima at 425nm and 585nm respectively. Beer's law is obeyed in the concentration range of 1-6 µg/ml and 2-12 µg/ml respectively. Spectrophotometric parameters were established for standardization of the methods including statistical analysis of data these methods have been successfully extended to the pharmaceutical formulations containing cabergoline.

 

MATERIALS AND METHODS:

All spectral measurements were done on Elico U.V. Visible Spectrophotometer. Analytical grade reagents were used and all solutions were prepared in double distilled water.

 

Preparation of alizarin red S (ARS):

Accurately weighed 200 mg of ARS was dissolved in 100 ml of distilled water,

 

Preparation of naphthol blue black (NBB):

Accurately weighed 200 mg of NBB was dissolved in 100 ml of distilled water.

 

Preparation of buffer solution:

Buffer solution was prepared by mixing 289 ml of 0.1M glycine solution (18.76 gm of glycine and 14.62 gm of NaCl were dissolved in 25ml distilled water) and 711 ml of 0.1M HCl and pH of the solution is adjusted to 1.5.

 

Preparation of standard drug solution:

About 100mgs of cabergoline was accurately weighed and dissolved in 10ml of 0.1N Hydrochloric acid in a 100 ml volumetric flask and diluted up to the mark with distilled water. The final concentration of cabergoline was brought to 50µg/ml with distilled water.

 

Method -I

Into a series of 125 ml separating funnels containing aliquots of standard CBL solution (0.5 –3.0 ml, 100mg/ml); 6 ml of 0.1M HCl solution and 2 ml of (3.2x10^-3M) of NBB solution were added. The total volume of aqueous phase in each separating funnel was adjusted to 15.0ml with distilled water.  To each separating funnel 10.0ml of chloroform was added and the contents were shaken for 2 min.  The two phases were allowed to separate and the absorbance of the separated chloroform layer was measured at 580nm against a similar reagent blank within the stability period (15 min-1hour).

 

Method-II

Into a series of 125 ml separating funnels containing aliquots of standard CBL solution (0.5-3.0ml, 50mg/ml); 6.0ml of 0.1 M HCI solution and 2.0ml of 0.2% dye solution (ARS) were added successively.  The total volume of aqueous phase in each separating funnel was adjusted to 15.0ml with distilled water.  To each separating funnel 10.0ml of chloroform was added and the contents were shaken for 2 min.  The two phases were allowed to separate and the absorbance of the separated chloroform layer was measured at l_max 420nm, against a similar reagent blank. 

 

RESULTS AND DISCUSSION:

The validation for given two spectrophotometric method development were performed using parameters like linearity, Accuracy, precision, limit of detection(LOD) limit of quantification(LOQ),  Beer's law limits, molar absorbivity, Sand ell’s sensitivity, %range of error and % relative standard deviation are summarized in Table 1. The regression analysis using the method of least squares was made for the slope(b),intercept(a) and correlation co-efficient (r) obtained from different concentrations are given in table 1. The results showed that these methods have reasonable precision.    The optimum conditions for colour development for methods I and II have been established by varying the parameters one at a time and keeping the other parameters fixed and observing the effects of product on the absorbance of the colored species.

 

To evaluate the validity and reproducibility of the methods, known amounts of pure drug were added to the previously analyzed pharmaceutical dosage forms and the mixtures were analyzed by the proposed methods.  The percent recoveries are given in Table - 2. The interference studies revealed that the common excipients and other additives that are usually present in the tablet dosage forms did not interfere at their regularly added levels

 

Beer's law plot of CBL-ARS(M1)method  

 

Beer's law plot of CBL-NBB (M2)method  

 

Table No -1. Optical regression characteristics, precision and accuracy of the proposed methods for cabergoline

Parameter	Method - I	Method - II
λmax(nm)	425nm	585nm
Beer's law limits (µg.ml-1)	1-6	2-12
Molar absorbivity (lit . mole-1,cm-1)	5.8 x 105	1.028x105
Sand ell’s sensitivity (µg.cm-2/0.001 abs. unit)	0.05354	0.03113
Regression equation (y*=a+bx) slope (b)	0.1284	0.0726
Intercept (a)	2.8 x 10-3	5 x 10-3
Correlation Co-efficient (r)	0.9999	0.9994
% R.S.D.	0.815	0.9561
% Range of error** (confidence limits)     0.05 level	1.2079	1.003
0.01 level	1.8948	1.574

*Y = a+ bx where x is the concentration of cabergoline in mg/ml and Y is the absorbance at the respective λmax.

** Average of six determinations considered.

   

Table No - 2. Assay of cabergoline in Pharmaceutical formulation

Formulation	Labelled amount in mg	Amount found by proposed   methods		% Recovery* by proposed methods
		MI	MII	MI	MII
Tablet - I	1	0.997	1.004	99.7	100.4
Tablet - II	1	0.992	0.998	99.2	99.8

*Recovery amount was the average of six determinations.

 

Conclusion:

The proposed methods are found to be simple, selective accurate and can be used in the estimation of cabergoline in pure and pharmaceutical dosage forms in a routine manner.

Acknowledgements:-The authors are thankful to the department of chemistry, Acharya Nagarjuna University- Dr. M.R. Appa Row Campus, Nuzvid for providing laboratory facilities.

 

REFERENCES:

1.     http://en.wikipedia.org/wiki/Cabergoline.

2.       Toshihiko Yoshida, Makoto Tanaka,Suzuki,Makoto Sohmiya and Koichi Okamoto, Antioxidant properties of cabergoline: inhibition of brain auto-oxidation and superoxide anion production of microglial cells in rats. Neuroscience letters,330, Issue 1(2002). 

3.       Onal A et al  Spectrophotometric determination of dopaminergic drugs used for Parkinson's disease, cabergoline and ropinirole, in pharmaceutical preparations Chem Pharm Bull (Tokyo). 2007 Apr;55(4):629

4.       M.S.Levi ; M.A.Brimble, Current medicinal chemistry, Vol II , No:18, pp2383 - 2397(15),Sep (2004) .

5.       Hutton J.J., Kolher W.D, Ahlskog J.E. et al, Multicenter, placebo-controlled trial of cabergoline taken once daily in the treatment of Parkinson's disease. Neurology  46:1062 –  1065,(1996)

6.       Destee A, Schneider E, Gershanik.O, Dom.R; Tichy  et al,  A dopamine agonist for the treatment of advanced Parkinson’s disease movement disorders  22(suppl - 1) ss 26-29 (1996). 

7.       Igarashi K. Hotta. K, Kasuya F, Abe. K, Sakoda. 5, J. Chromatograph. B; Anah Tech. Determination of cabergoline and L-dopa in human plasma using liquid chromatography-tandem mass spectrometry.  Bio - med lif. sci., 792(1) 55-61(July 2003).

 

 

Received on 07.12.2011         Modified on 26.12.2011

Accepted on 03.01.2012         © AJRC All right reserved