ЖУРНАЛ АНАЛИТИЧЕСКОЙ ХИМИИ, 2007, том 62, № 5, с. 481-486
^=ОРИГИНАЛЬНЫЕ СТАТЬИ
УДК 543
SENSITIVE BROMATOMETRIC METHODS FOR THE DETERMINATION OF SALBUTAMOL SULPHATE IN PHARMACEUTICALS
© 2007 r. B. C. Somashekar, K. Basavaiah
Department of Chemistry, Univesity of Mysore Manasagangotri, Mysore-570006, India Received 13.02.2006; in final form, 06.09.2006
The proposed methods provide semi micro and micro level determination of salbutamol sulphate (SBS) in authentic sample and in dosage forms. The spectrophotometric method is much more sensitive than most of the procedures known for the determination of SBS. The titrimetric method takes less than 15 min for analysis. All the procedures are simple and do not need elaborated treatment and tedious extractions.
One titrimetric and two spectrophotometric methods are described for the assay of SBS using bromate-bromide mixture and two dyes, rhodamine B and methylene blue, as reagents. In titrimetry, an aqueous solution of SBS is treated with a measured excess of bromate-bromide mixture in HCl medium, followed by iodometric determination of unreacted bromine. Spectrophotometric methods involve the addition a known excess of bromate-bromide mixture to SBS in acid medium, followed by the determination of residual bromine by reacting with either a fixed amount of rhodamine-B and measuring the absorbance at 555 nm (Method A) or methylene blue and measuring the absorbance at 665 nm (Method B). In all the methods, the amount of in situ generated bromine reacted corresponds to the amount of SBS. Titrimetric method is applicable over 3.0-8.0 mg range and the reaction stoichiometry is found to be 1:2 (SBS: KBrO3). In spectrophotometric methods, the absorbance is found to increase linearly with the concentration of SBS which is corroborated by the correlation coefficient of 0.9978 and 0.9991 for method A and method B, respectively. The systems obey Beer's law for 0.25-2.5 |g/mL (Method A) and 0.75-7.5 |g/mL (Method B). The calculated apparent molar absorptivity values are found to be 8.96 x 104 and 4.67 x 104 l mol-1 cm-1, for method A and method B, respectively, and the corresponding Sandell sensitivity values are 6.43 and 12.34 ng/cm2. The limits of detection and quantification are also reported for both spectrophotometric methods. Intra-day and inter-day precision and accuracy of the methods were evaluated. The methods were successfully applied to the assay of SBS in tablet and capsule preparations and the results were compared with those of a reference method by applying Student's t- and F-tests. No interference was observed from common pharmaceutical ajuvants.
Salbutamol sulphate (structure is given in Figure 1) is a selective beta-2-agoinst antiasthmatic. Its primary action is to stimulate adenyl cyclase which catalyses the formation of cyclic adenocin monophosphate (AMP). The cyclic AMP thus formed mediates smooth muscle relaxation and branchodilation. Among the techniques reported for the determination SBS in pharmaceuticals, methods using high performance liquid chromatography (HPLC) [1-7] are tedious, time-consuming, and require special and expensive apparatus. Besides, all the reported HPLC methods are relatively insensitive. The other chromatographic method, thin-layer chromatography [8], although simpler than HPLC methods, is also less sensitive with the linear range being 20-580 ^g/mL. Non-chromatographic methods such as derivative ultra-violet spectrophotometry [9], derivative difference spectrophotometry [10], capillary electrophoresis [11] and a-c oscillopolarography [12] are also relatively complicated in terms of assay procedure or equipment required for analysis.
photometry, and procedures based on such varied reactions as redox [13, 14], reduction followed by chelation [15], oxidative coupling [16, 17], diazotization and coupling [18, 19], nitrosation [20], nitration [21], nitration followed by Meiscnheiner complex formation [22] and charge-transfer complex formation [23] are found in literature. However, many of these procedures suffer from one or the other disadvantage (Table 1) such as
OH
HO
H3C
OH
OH
I
O=S-OH
II
O
The most widely used technique for the assay of SBS in pharmaceuticals has been the visible spectro-
Structure of salbutamol sulphate.
2
Table 1. Comparison of reported spectrophotometry methods with the proposed method for the assay of SBS
Reagent/s used W nm Beer's Law limit |g/mL Molar absorptivity, l mol-1 cm-1 Remarks Reference
F-C reagent* 760 0.0-6.0 - - [13]
F-C reagent* 750 1-15 - Uses on-line solid phase extraction and flow injection analysis apparatus [14]
Iron(III)-1,10-phenanthroline 510 400-4000 - Least sensitive [15]
Ferricyanide-4-aminophenazone 505 25-175 - Involves heating; waiting time of 30 min [16]
Cerium(IV)-MBTH* 530 Upto 15 2.4 x 104 Involves extraction and an expensive reagent [17]
NaNO2-PHSA 440 Upto 10 - - [18]
NaNO2-3-amino pyridine 440 1-10 - - [19]
NaNO2 410 5-60 - Involves boiling for 30 min [20]
KNO3-H2SO4 420 0-48 - Involves boiling for 30 min [21]
HN O- H2SO4/Meisenheimer 386 4.8-16.0 - Involves boiling for 20 min [22]
complex formation
DCQO* 1-30 - Uses organic solvent [23]
TCNQ* 2-20 - Uses organic solvent [23]
Br O3 -Br-/ a) Rhodamine-B, and 555 0.25-2.5 8.96 x 104 No heating, extraction step involved. Present methods
b) Indigo carmine 665 0.7-7.5 4.67 x 104
* F-C reagent - Folin-Ciocalteu reagent. (MBTH - 3-methyl benzothiazolin-2-one hydrozone, PHSA - Phenylhydrazine sulphonic acid, DCQ - 2,6-dichloroquinone chlorimide, TCNQ - 7,7,8,8-tetracyano quinodimethane).
poor sensitivity, heating or extraction step, critical working conditions or the use of organic solvents; and hence are unsatisfactory for routine analysis. The only visual titrimetric method [24] reported employs N-bro-mosuccinimide as the oxidimetric titrant which is unstable in solution and requires daily standardization [25]. Recently Issa et al. [26] have reported a conduc-tometric titration method using phosphotungstic and phospho molybdic acids as titrants. Even these procedures are time consuming and less sensitive.
This paper describes three assay methods for SBS in tablets and capsules. The methods are based on two techniques and employ bromate-bromide, rhodamine-B and methylene blue dye as reagents. The proposed methods have the advantages of being rapid and simple and are free from interference from common tablet and capsule excipients. The results obtained were closely comparable to those of a reported method, and recovery tests were also found to be satisfactory.
EXPERIMENTAL
Apparatus. A Systronics model 106 digital spectrophotometer with 1-cm matched quartz cells was used for the absorbance measurements.
Reagents and materials. All chemicals used were of analytical reagent grade. Double distilled water was used throughout the investigation. Bromate-bromide reagent solution (5 mM KBrO3 - 50 mM KBr) was prepared by dissolving accurately weighed 0.8 g of KBrO3 (Sarabhai M. Chem, India) and 6 g of KBr (IDPL, India) in water and diluting to 1 litre in a calibrated flask and used in titrimetric work. A 0.03 M sodium thiosul-phate solution was prepared by dissolving about 7.5 g of the salt (Sisco Chem Industries, India) in 1 litre of water. Aqueous solutions of 10% potassium iodide and 1% starch indicator were prepared in the usual manner. For spectrophotometry investigations, a bromate-bro-mide solution equivalent to 1000 Mg/mL KBrO3 and 10-fold excess of KBr was prepared by dissolving accurately weighed 100 mg of KBrO3 and 1 g of KBr in water and diluting to the mark in a 100 mL calibrated flask. This was then diluted stepwise to obtain working concentrations of 10 and 25 Mg/mL KBrO3 for use in the method A and method B, respectively. A 1000 Mg/mL methylene blue solution was prepared by dissolving 143 mg of dye (S.d. Fine Chem, India, dye content 70%) in water and diluting to 100 mL in a calibrated flask and then further diluted to get a working concentration of 40 Mg/mL. Rhodamine-B solution (500 Mg/mL)
was first prepared by dissolving 62.5 mg of dye (S. d. Fine Chem, India, dye content 80%) in water and diluting to 100 mL in a calibrated flask and then diluted appropriately to get a working concentration of 50 |g/mL dye solution. HCl (5M) was prepared by diluting 443 mL of concentrated acid (Qualigens Fine Chem. India sp. gr. 1.18) to 1 litre with water, and this was further diluted to get 1 M acid for titrimetric work. Pharmaceutical grade SBS was kindly provided by Cipla India Ltd, Mumbai, India and was used as received. A 1mg/mL pure drug solution was prepared in water and used in titrimetric work. This solution (1000 |g/mL SBS) was diluted appropriately with water to yield working concentrations of 5 and 15 |g/mL for spectrophotometry method A and method B, respectively.
Analytical procedures. Titrimetry: A 10 mL aliquot of pure drug solution (3.0-8.0 mg SBS) was accurately measured and transferred into a 100 mL titration flask, and the solution was acidified by adding 5 mL of 1 M HCl. 10 mL of bromate-bromide solution (5 mM KBrO3 - 50 mM KBr) were pipetted into the flask, the flask was stoppered, the contents were mixed well and let stand for 15 min with occasional swirling. Finally, 5 mL of 10% potassium iodide solution were added and the liberated iodine titrated with 0.03 M thiosulphate solution using starch indicator. A blank titration was performed under similar conditions. From the amount of bromate reacted, the amount of SBS in the measured aliquot was calculated.
Spectrophotometric method A: different aliquots (0.5, 1.0...5.0 mL) of standard 5 |g/mL SBS solution were delivered into a series of 10 mL calibrated flasks by means of a micro burette and the total volume was adjusted to 5 mL by adding water. To each flask 1 mL of 5 M HCl and 7 mL of KBrO3-KBr solution (10 |g/mL KBrO3) were added. The flasks were stoppered, contents were mixed and let stand for 15 min with
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