ЖУРНАЛ АНАЛИТИЧЕСКОЙ ХИМИИ, 2013, том 68, № 11, с. 1084-1091
ОРИГИНАЛЬНЫЕ СТАТЬИ
УДК 543
SENSITIVE AND SELECTIVE SPECTROPHOTOMETRIC METHODS FOR THE DETERMINATION OF PHENIRAMINE MALEATE IN BULK DRUG AND IN ITS FORMULATIONS USING SODIUM HYPOCHLORITE © 2013 M. S. Raghu, K. Basavaiah, Sameer A. M. Abdulrahaman, K. N. Prashanth, K. B. Vinay
Department of Chemistry, University of Mysore, Manasagangotri Mysore 570006, Karnataka, India Received 24.05.2011; in final form 20.06.2012
Two simple, selective and sensitive spectrophotometric methods are described for the determination of phe-niramine maleate (PAM) in pure and dosage forms. The method is based on the reaction of PAM with hypochlorite in the presence of Kolthoff buffer (phosphate-borate) of pH 7.0 to form the chloro derivative of PAM, destruction of the excess hypochlorite by nitrite ion (the chloro derivative of drug is unaffected under the
optimized conditions) followed by the oxidation of iodide with the chloro derivative of PAM to iodine (i-) which
is either measured directly at 355 (method A) or reacted with starch to form a blue chromogen measurable at 590 nm (method B). The optimum conditions that affect the reaction were ascertained, and under these conditions linear relationship was obtained in the concentration ranges of 2—50 and 1—25 ^g/mL PAM in methods A and B, respectively. The calculated molar absorptivity values are 7.26 x 103 and 1.28 x 104 L/mol cm for method A and method B, respectively. Sandell's sensitivity values, limits of detection (LOD) and quantification (LOQ) are calculated as per ICH guidelines. The proposed methods were applied successfully to the determination of PAM in tablets and injection with good accuracy and precision and without interferences from common additives. The results obtained by the proposed methods were compared favourably with those of the reference method. The accuracy and reliability of the proposed methods were further checked by recovery studies via standard addition procedure.
Keywords: pheniramine maleate, spectrophotometry, sodium hypochlorite, pharmaceuticals.
DOI: 10.7868/S0044450213110133
Pheniramine maleate (PAM) (C16H20N2 • C4H4O4), chemically known as N,N-dimethyl-3-phenyl-3-(2-pyridyl)propylamine hydrogen maleate is an antihistamine H1 receptor antagonist used as antihistaminic drug for the symptomatic relief ofhypersensitivity reaction. It inhibits the effect of histamine on capillary permeability and on vascular, bronchial and many other types of smooth muscle. It is used in allergic conditions, itching and mainly to prevent motion sickness, nausea and vomiting [1]. The determination of micro amounts of PAM in pharmaceutical preparation is very important for medical and pharmaceutical needs. Therefore, it is necessary to develop simple, selective, sensitive and cost-effective methods for the determination of micro amounts of PAM in pharmaceuticals.
There are several reports on determination of PAM in pharmaceuticals. PAM is official in United States Pharmacopeia [2] and British Pharmacopoeia [3] which describe non-aqueous titration with perchloric acid as titrant where the end point was located either visually using crystal violet as indicator [2] or potenti-ometrically [3].
Determination of PAM in pharmaceuticals including bulk drug, tablets, injections, expectorants, syrups and nasal spray involves several techniques such as HPLC [4, 5], polarography [6], capillary zone electrophoresis [7] flow injection analysis [8], UVspectro-photometry [9] and visible spectrophotometry [10].
Sodium hypochlorite has been used for the assay of many organic compounds of pharmaceutical interest [11—13]. The reaction between hypochlorite and PAM has not been investigated yet.
The aim of the present work was to develop simple, selective and sensitive spectrophotometric methods for the determination of PAM in bulk drug as well as in dosage forms using sodium hypochlorite. The methods are based on the chlorination reaction of PAM through its amino group with hypochlorite in the presence of Kolthoff buffer (phosphate-borate) of pH 7.0, destruction of the excess hypochlorite by nitrite ion and reacting of the chloro derivative of PAM with iodide to liberate iodine which is either measured directly at 355 nm or reacted with starch followed by the measurement of starch-iodine chromogen at 590 nm.
EXPERIMENTAL
Instrument. A Systronics model 106 digital spectrophotometer (Systronics, Ahmedabad, Gujarat, India) equipped with 1 cm matched quartz cells was used for all absorbance measurements.
Materials. Pharmaceutical grade pheniramine maleate (PAM) certified to be 99.85% pure was received from Sanofi Aventis Pharma, Mumbai, India. The following pharmaceutical preparations were purchased from commercial sources in the local market and subjected to analysis: Avil 25 and 50 mg tablets and Avil injection (all from-Aventis Pharma Limited, Tarapur, Thane, India).
Reagents and chemicals. All the reagents used were of analytical-reagent grade and distilled water was used throughout the investigation.
Stock standard solution of PAM. A stock standard solution equivalent to 200 ^g/mL of PAM was prepared by dissolving accurately weighed 20 mg of pure drug in water and diluted to the mark with water in a 100 mL calibrated flask. The stock standard solution was diluted appropriately with the water to get a working concentration of100 and 50 ^g/mL PAM solution for method A and method B, respectively, before being used.
Sodium hypochlorite solution (0.012 M). A 2.0 mL of the chemical (Merck, Mumbai, India, available chlorine ~4% w/v) was diluted with water to the mark in a 100 mL calibrated flask and standardized iodo-metrically [14].
Sodium nitrite (0.04M). An amount (276 mg) of the chemical (Merck, Mumbai, India) was dissolved in water, transferred into a 100 mL calibrated flask and diluted to the mark with water.
Kolthoff buffer of pH 7.0. A buffer solution ofpH 7.0 was prepared by mixing 62.3 mL of 0.1 M potassium dihydrogen phosphate (S. D. Fine Chem. Ltd., Mumbai, India) and 37.3 mL of 0.05 M borax (S. D. Fine Chem. Ltd., Mumbai, India), and the pH was adjusted with a pH meter using these solutions.
Starch-potassium iodide reagent (SKI). A 750 mg of starch soluble (Loba Chemie PVT Ltd., Mumbai, India) was dissolved in 100 mL boiling water and after 5 min 1.0 g ofpotassium iodide (Merck, Mumbai, India) was added slowly to the same solution and the boiling was continued for an additional 5 min. This solution, when protected from light and stored at 10°C when not in use, remained colorless for several weeks [15].
Potassium iodide (2%) (KI). Aqueous solution of the reagent (Loba Chemie PVT Ltd, Mumbai, India) was prepared just prior to usage and used in method A.
General procedures. Method A. Different aliquots (0.2, 0.5, 1.0, ..., 5.0 mL) of a standard PAM solution (100 ^g/mL) were accurately transferred into a series of 10 mL standard flasks and the total volume was adjusted to 5.0 mL by adding a suitable volume of water. To each flask, 1.0 mL each of Kolthoff buffer (phos-
phate-borate) of pH 7.0, 0.012 M hypochlorite solution and 0.04 M sodium nitrite solution were added. After one minute, 1.0 mL of 2% potassium iodide was added and the absorbance of resulting yellow colored solution was measured at 355 nm against the reagent blank prepared in the same manner without adding drug solution.
Method B. Varying aliquots of standard PAM solution equivalent to 1—25 ^g/mL (0.2—5.0 mL of 50 ^g/mL) were accurately transferred into a series of 10 mL standard flasks and the total volume in each flask was brought to 5 mL by adding suitable volume of water. To each flask, 1.0 mL each of Kolthoff buffer (phosphate-borate) of pH 7.0, 0.012 M hypochlorite solution and 0.04 M sodium nitrite solution were added. After one minute, 1.0 mL of starch-iodide reagent was added, and the absorbance of the resulting blue colored solution was measured at 590 nm against the blank.
Procedure for formulations tablets. Twenty tablets were accurately weighed and powdered. A portion equivalent to 20 mg PAM was accurately weighed and transferred into 100 mL volumetric flasks, 70 mL of water was added and shaken for about 20 min. Then, the volume was made up to the mark with water, mixed well and filtered using Whatmann No. 42 filter paper. The first 10 mL portion of the filtrate was discarded. An aliquot of the filtrate (200 ^g/mL in PAM) was further diluted to 100 and 50 ^g/mL solutions with water and used for the assay of PAM in method A and method B, respectively, by following the procedures described earlier.
Injections. Contents of ten injection ampoules were withdrawn and mixed together. One mL of mixed injection solution equivalent to 22.75 mg of PAM was accurately measured and transferred in to 100 mL volumetric flask, 70 mL of water was added and shaken well. Then the volume was made up to the mark with water The resulting 227.5 ^g/mL PAM solution was diluted appropriately to get 100 and 50 ^g/mL solutions with water and used for the assay in method A and B, respectively. A suitable aliquot was next subjected to analysis by following general procedure as described earlier.
Placebo blank analysis. A placebo blank of the composition: talc (15 mg), starch (5 mg), acacia (5 mg), methyl cellulose (15 mg), sodium citrate (5 mg), magnesium stearate (15 mg) and sodium alginate (5 mg) was made and its solution was prepared as described under 'Procedure for tablets' and then analyzed using the procedures described above.
Procedure for the determination of PAM in synthetic mixture. To the placebo blank of the composition described above, 20 mg of PAM was added and homogenized, transferred to 100 mL volumetric flask and the solution was prepared as described under "Procedure for tablets". A convenient aliquot was diluted and then subjected to analysis by the procedures described
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