INTRODUCTION:

Terbutaline sulphate is chemically 5-[2-(tert-butylamino)-1-hydroxyethyl] benzene-1,3-diol sulphate. Terbutaline sulphate used for the prevention and reversal of bronchospasm in patients 12 years of age and older, with reversible, obstructive airway disease, as well as symptomatic management of reversible bronchospasm associated with bronchitis and emphysema. Also used acute IV and sub-Q therapy in selected women to inhibit uterine contractions in preterm labor (tocolysis) and prolong gestation when beneficial.

Terbutaline sulfate, USP is a white to gray-white crystalline powder. It is odorless or has a faint odor of acetic acid. It is soluble in water and in 0.1N hydrochloric acid, slightly soluble in methanol, and insoluble in chloroform.

Its molecular weight is 548.65. Literature survey reveals the spectrophotometric^1-3, HPLC^4-11 and HPTLC¹²methods for the estimation of terbutaline sulphate. Simple, rapid and reliable no aqueous titration method is developed for the determination of terbutaline sulphate. This method can be used for the routine analysis. In the proposed methods optimization and validation of this method are reported.

Structure of Terbutaline sulphate:

EXPERIMENTAL:

Instrumentation:

An potentiometric titrator was used (Lab- India-Auto titrator) for assay method development and validation.

A Shimadzu analytical balance with 0.01 mg was used.

Reagents and chemical:

Reference standard of terbutaline sulphate was obtained from reputed firm with certificate of analysis.

Potassium hydrogen phthalate, perchloric acid, mercury acetate and glacial acetic acid of A. R. grade were used.

General procedure:

Standardization of 0.1 N perchloric acid:

About 0.350 mg of potassium hydrogen phthalate (previously powdered lightly, dried at 120^oC for 2 hours) was weighed accurately into clean and dry titration jar. It was dissolved in 50 ml of glacial acetic acid. It was titrated with 0.1 N perchloric acid by using auto titrator. Blank determination was performed out for necessary correction. The titration was performed in duplicate.

One ml of 0.1 N HClO₄ is equivalent to 0.2042 gm of potassium hydrogen phthalate (C₈H₅KO₄)

Normality of perchloric acid = –––––––––––––––

B.R. x 0.2042

Where W is weight of potassium hydrogen phthalate in g. B.R. is burette reading in ml.

Quantitative determination of Terbutaline sulphate:

About 0.400g. of terbutaline sulphate test sample was weighted accurately into a clean and dried titration jar. It was dissolved in 60ml. of anhydrous glacial acetic acid. It was heated to dissolve terbutaline sulphate and 15 ml of 5% (w/v) mercuric acetate was added.

It was titrated with 0.1N perchloric acid potentiometrically.

Blank determination was also carried out for necessary correction.

One ml of 1 N perchloric acid is equivalent to 0.05486 g. of terbutaline sulphate

% (Percentage) Terbutaline sulphate on the dried basis was calculated as below.

B.R. x N x 0.05486 x 100 x 100

% assay = –––––––––––––––––––––––––––––––––––

W x 0.1

Where

B.R. is burette reading in ml at the potentiometric end point.

N is actual normality of 0.1 N perchloric acid.

W is weight of the sample taken in g.

RESULT AND DISCUSSION:

Determination of terbutaline sulphate:

The objective of this work was to determine accurately the content of terbutaline sulphate. The assay of terbutaline sulphate (on the dried basis) of various batches of test sample was analyzed using the above method. It was in the range of 99.39 to 99.64 %.

Analytical method validation:

The method precision was checked after analyzing six different preparations of homogeneous test sample of terbutaline sulphate. The % RSD of results obtained was found to be 0.1144. It confirms good precision of the method. The results are presented in table 1.

Table no. 1: Method of precision

Sr. No	Weight of Terbutaline sulphate	Burette reading in ml	Normality of perchloric acid	% assay
1	0.40572	7.3087	0.1009	99.74
2	0.40599	7.3146	0.1009	99.76
3	0.40583	7.3305	0.1009	100.02
4	0.40598	7.3188	0.1009	99.820
5	0.40580	7.3151	0.1009	99.821
6	0.40594	7.3286	0.1009	99.971
			Mean	99.855
			Std. Deviation	0.1142
			RSD	0.1144

Linearity:

For the establishment of method linearity, five different weights of terbutaline sulphate test samples corresponding to 50 %, 80 %, 100 % 120% and 150% of the about weight (0.405g.) were taken and analyzed for % (percentage) of terbutaline sulphate content. The results are in table 2.

Table no.2: Linearity

Sr. No.	Weight of Terbutaline sulphate in gm	Burette reading	Normality of Perchloric acid	% assay
1	0.2026	3.6573	0.1009	99.92
2	0.3244	5.854	0.1009	99.88
3	0.4054	7.315	0.1009	99.87
4	0.4864	8.764	0.1009	99.73
5	0.6082	10.954	0.1009	99.69
			Mean	99.82
			Std. Deviation	0.1018
			RSD	0.1022

The potentiometric titration was conducted once at each level. Linearity curve Figure no .1 was drawn by plotting test sample weight in gram on x axis and titre values on y axis.

Fig. no.1: Linearity curve

The values of correlation coefficient, slope and intercept are given in table 3.

Table no.3: Regression values:

Parameter	Values
Slope	17.99
Intercept	0.015
Coefficient of co-relation	0.9999

Accuracy and recovery:

Accuracy was determined at five different levels i.e., 50 %, 80%, 100%, 120% and 150% of the nominal concentration. (0.400g.) The titration was conducted in triplicate at each level and the titre value was recorded. The tire value obtained in linearity study was considered as true value during the calculation of percentage (%) recovery. The percentage recovery is calculated using following equation.

Titre value x 100

Percentage recovery = ---------------------------

True titre value

The percentage range recovery of Terbutaline sulphate was in 99.39 to 99.64 %. It confirms the accuracy of the proposed method. (Table 4).

Table no 4: accuracy and precision

Level no.	Weight of Terbutaline sulphate added	Weight of Terbutaline sulphate found	% assay	Mean % assay
1	0.2027	0.2020311	99.67	99.65
	0.2030	0.2020053	99.51
	0.2025	0.2020748	99.79
2	0.32448	0.32298739	99.54	99.63
	0.32437	0.32265084	99.47
	0.32430	0.3239757	99.90
3	0.40545	0.40269294	99.32	99.39
	0.40587	0.40315067	99.33
	0.40588	0.40401295	99.54
4	0.48649	0.48396025	99.48	99.59
	0.408666	0.40772607	99.77
	0.48661	0.48432293	99.53
5	0.60821	0.60535141	99.53	99.64
	0.60827	0.60626271	99.67
	0.60822	0.60651698	99.72

Ruggedness:

The ruggedness of the method is defined as degree of reproducibility of results obtained by analysis of terbutaline sulphate sample under variety of normal test conditions such as different laboratories, different analysts and different lots of reagents. Quantitative determination of terbutaline sulphate was conducted potentiometrically on one laboratory. It was again tested in another laboratory using different instrument by different analyst. The assays obtained in two different laboratories were well in agreement. It proved ruggedness of the proposed method.

CONCLUSION:

The proposed method of non-aqueous potentiometric titration was found to be precise, accurate and rugged. The values of percentage recovery and standard deviation showed sensitivity. The method was completely validated. It showed satisfactory data for all the parameters of validation. Hence it can be applied for routine quality control application.

REFERENCES:

1. A. Anton Smith, R. Manavalan and K. Sridhar. Spectrophotometric estimation of terbutaline sulphate in pharmaceutical dosage forms. International Research Journal of Pharmacy, 1 (1); 2010: 213-219.

2. Mohamed Y. Dhamra, Theia'a N. Al-Sabha and Thabit S. Al-Ghabsha. Spectrophotometric Determination of Terbutaline Sulphate and tetracycline Hydrochloride via ion pair Complex Formation Using Eosin Y. Pak. J. Anal. Environ. Chem. 15(1); 2014: 84 – 92.

3. E. Onur. A. Yesilada. Second and fourth derivative spectrophotometric determination of turbualine sulphate and glyceryl guaiacolate in expectorant syrup. FABAD Journal of Pharmaceutical Science, 19; 1994: 57-63.

4. Prabha Thangavelu, Arul Caroline Grace, Jagadeeswaran Murugesan. Analytical method development and validation for the simultaneous estimation of salbutamol sulphate, guaifenesin, and ambroxol hydrochloride by RP-HPLC method in commercial oral liquid dosage form. International Journal of Pharmaceutical Sciences and Research.10(1) 2019;): 260-265.

5. Satyanarayana.P.V.V.1, Murali. M., Venkateswara Rao. P. Simultaneous determination of terbutaline and bromhexine in combined pharmaceutical dosage form by RP-HPLC method. International Journal of Chem Tech Research. 4(1) ;2012: 240-246.

6. Senthilraja M. g Giriraj P. Reverse phase HPLC method for the simultaneous estimation of terbutanile sulphate, bromhexine HCL and guaifenesin in cough syrup. Asian Journal of Pharmaceutical and Clinical Research.4(2); 2011:13-15.

7. Giriraj, P. Rajavel, M. Subapriya, K. Manikandan, K. Radhakrishnan, CH. Koteswara Rao. Simultaneous estimation and method validation of Terbutaline sulfate and Guaifenesin in liquid dosage form by RP-HPLC. Journal of Pharmacy Research. 5(2);2012: 746-748.

8. Jaiprakash N Sangshetti, Gayatri Takate, Rana Z. Ahmed, Zahid Zaheer. Method Development and Validation of RP-HPLC Method for the Simultaneous Estimation of Terbutaline Sulphate and Guaiphenesin in Bulk and Tablet Dosage Form. Journal of Chemical and Pharmaceutical Research, 9(1); 2017:100-107.

9. Gananadhamu Samanthula, Krishnaveni Yadiki, Shantikumar Saladi, Sreekanth Gutala , K. V. Surendranath. Stability-Indicating RP-HPLC method for the simultaneous estimation of doxofylline and terbutaline sulphate in pharmaceutical formulations. Scientia Pharmaceutica. 81; 2013:969-982.

10. A. Porel, Sanjukta haty, A. Kundu. Stability-indicating HPLC method for simultaneous determination of terbutaline sulphate, bromhexine hydrochloride and guaifenesin. Indian Journal of Pharmaceutical Sciences., 73 (1); 2011: 46-56.

11. B. Sunandana, K. Sushmitha, Buchi N. Nalluri. RP-HPLC-PDA method for the analysis of terbutaline sulphate in bulk, dosage forms and in dissolution samples. Journal of Applied Pharmaceutical Science. 3 (03) ; 2013:126-132 .

12. Md. Faiyazuddin, Sayeed Ahmad, Zeenat iqbal, Sushma Talegaonkar, Farhan Jalees Ahmad, Aseem Bhatnagar, Roop Krishen Khar. Stability indicating HPTLC method for determination of terbutaline Sulfate in bulk and from Sub micronized dry Powder inhalers. Analytical Sciences .26; 2010: 457-472.

Received on 14.12.2019 Modified on 12.01.2020

Asian J. Research Chem. 2020; 13(2):82-84.

DOI: 10.5958/0974-4150.2020.00017.6