Bromometric determination of some pharmaceutically important antimony(III) compounds

MICROCHEMICAL

JOURNAL

41, 34&347 (1990)

Bromometric Determination of Some Pharmaceutically Important Antimony(lll) Compounds F. BELAL,’

F. IBRAHIM,

AND A. EL-BRASHY

Department of Analytical Chemistry, Faculty of Pharmacy, Universi@ of Mansoura, Mansoura 35516, Egypt Received July 31, 1989; accepted September 18, 1989 A titrimetric method for the determination of some antimony(III) compounds of pharmaceutical interest is described. The method involves the use of 1,3-dibromo-3,Mimethylhydantoin as an oxidomettic titrant. The location of the endpoint could be accomplished by any of three techniques: visually, using diierent dyestuffs, e.g., methyl red, methyl orange, amaranth, or indigotine; potentiometrically, using a platinumkalomel electrode system; or spectrophotometrically. The stoichiometry of the reaction pathway was assessed. The proposed method was applied to the determination of the studied compounds in dosage forms and the results obtained compared favorably to those obtained with the official methods. 0 1990Acadcmi~ RUSS. IDC.

INTRODUCTION Antimony(II1) compounds are of great importance in various fields, particularly in medicine and the textile industry. The main therapeutic use of antimony compounds is in the treatment of schistosomiasis and filariasis. The majority of the methods available for the determination of antimony(II1) compounds are either complicated, e.g., coulometry (I), X-ray fluorescence spectroscopy (2), radiometry (3), atomic absorption spectroscopy (4), and polarography (5), or not sufficiently sensitive, e.g., gravimetry (6). The oxidometric methods reported suffer several limitations. In the method that uses potassium dichromate as an oxidometric titrant, the reaction is too slow, taking 2-3 h, and the endpoint is not sharp (7). The method has been modified (8) using diphenylamine as an indicator and iodine as a catalyst; however, it still suffers the following drawbacks: the working acidity is critical and limited to 2-5 M sulfuric acid; the color change at the endpoint is not clear; moreover, the method is not applicable to dilute solutions (0.01 M). Less desirable oxidizing titrants for antimony(II1) are permanganate, iodate, and bromate; the difficulties encountered with them are well documented (7). Titration with cerium(IV) sulfate and diphenylamine as indicators also has a slow indicator reaction, despite the use of iodine as a catalyst (9). Potassium hexacyanoferrate was proposed for the oxidimetric titration of antimony(II1) compounds. Fresno and Valdes (10) performed the titration potentiometrically at 50-70°C in concentrated sodium hydroxide, while Kiboku (II) carried it out indirectly after precipitation of antimony as ’ To whom correspondence should be addressed at present address: Institut fiir Pharmazeutische Chemie, George Voigt Strasse 14, Frankfurt Universimt, D-6000 Frankfurt/Main 11, FRG. 340 0026265x/90

$1.50

cOpyi& Q 1990 by Academic F’ms, Inc. Au Iigbts of rcprodluxion in my f‘xm reserved.

BROMOMETRIC

DETERMINATION

OF

Sb(II1)

COMPOUNDS

341

its sulfide. Zhdanov and Kurochkina (12) studied the amperometric titration, and concluded that the results are erroneous and it-reproducible. Recently, Nbromosuccinimide (13) was used for the determination of some antibilharzial antimony(II1) compounds through direct and indirect titration. N-Bromosuccinimide failed to give satisfactory results; moreover, the titrant is unstable and should be checked daily. It is thus clear that there is still a need for a simple chemical method for the analysis of antimony(II1) compounds. In this report, 1,3-dibromo-3,5dimethylhydantoin (DBH) is proposed as an oxidometric titrant for some pharmaceutically important antimony(II1) compounds. The reagent is characterized by its stability: a solution containing 2% DMF keeps its titer for about 1 month. Work from our laboratory resulted in successful applications of DBH to the determination of a vast number of pharmaceuticals (14-17). The purpose of the present work is to study the reaction of DBH with some antimony(II1) compounds in an attempt to develop a simple and reliable method for the determination of these compounds in dosage forms. EXPERIMENTAL Apparatus

1. Spectrophotometer: Pye Unicam, SP 1800. 2. pH meter: Pye Unicam, Model 292, equipped with platinum/calomel electrode system. Reagents

1. DBH: Aldrich; a 5 x 10m3M solution is prepared by dissolving 1.43 g of the pure and crystallized compound in the smallest possible volume of hot water, cooling, diluting to about 900 ml with water, adding 20 ml of DMF, and completing the volume to 1 liter with water and standardized iodometrically. 2. Indicator solutions: 0.1% ethanolic solutions of methyl red, methyl orange, amaranth, and indigotine. Sample Preparation

Solutions (0.1% and 0.005 M) of the studied compounds were prepared in 10% HCl (w/v). If the solution becomes turbid, hydrochloric acid is added until the precipitate just redissolves. Procedures

1. Visual titration. Transfer an accurately measured volume of the sample solution containing a suitable quantity of the analyte to a small flask, and add 2-3 drops of any of the indicator solutions. Titrate with a 5 x 10m3M solution of DBH to the discharge of the color of the indicator. A blank is carried out and its value is deduced from the endpoint. 2. Potentiometric titration. Transfer an accurately measured volume of the sample containing a convenient quantity of the analyte to the titration cell. Dilute to about 50 ml with 10% HCI (w/v) and titrate with standard DBH. The titrant is

342

BELAL,

IBBAHIM,

AND

EL-BBASHY

added in small increments differing by 0.5 ml and the potential E (mV) is measured after each addition and plotted versus the volume V (ml) of the titrant. The location of the endpoint is easily obtained from the titration curve E vs V or from the first derivative curve AEIAV vs V. 3. Spectrophotometric titration. Transfer aliquots of the sample solution to each of 15 25ml measuring flasks, except for the first flask. The titrant is added to each succeeding flask in increasing increments differing by 1.0 ml, followed by sufficient 10% HCl (w/v) to bring the volume to the mark. The absorbance at 345 nm is measured against water as a blank. The absorbance A is plotted against the volume V of the titrant; two straight lines are produced, the intersection of which corresponds to the endpoint. Assay Procedure for Dosage Forms A. For the ampoules. Mix the contents of 20 ampoules. Transfer an accurately measured volume of the mixed solution to a 250~ml volumetric flask, so that the final concentration is about 1 .O mg - ml- ‘. Apply procedure 1, 2, or 3. B. Assay procedure for vials. Mix the contents of 20 vials. Transfer 100 mg, accurately weighed, of the powder to a 100~ml volumetric flask, dissolve in 10% HCl (w/v), and complete to the mark with the same solvent. Apply procedure 1, 2, or 3. Calculation Calculate

the amount of the drug from amount of the drug (mg) = VMRIN,

where V M R N

= = = =

ml of DBH solution, molecular weight of the drug, molarity of DBH, number of moles of DBH per mole of the sample. DISCUSSION

Table 1 shows the results of the analysis of the compounds studied using the visual method for the detection of the endpoint. Four different dyestuffs were tried and all proved to be equally satisfactory. The titrant preferentially oxidizes the substrate until the endpoint is reached; it irreversibly oxidizes the indicator with a consequent decolorization. The value of the blank does not exceed 0.1 ml of the titrant for 2 drops of any of the indicators. Table 2 lists the results of the determination of the antimony(II1) compounds using spectrophotometric and potentiometric titrations. In the spectrophotometric technique, the titrant is added in increasing increments and the corresponding absorbance is measured at 345 nm. At this wavelength, no interference is noticed from either the drug or the reaction products. Figure 1 shows a typical titration curve of astiban with DBH. This technique offers the advantage of being applicable to small concentrations of the drugs.

BROMOMETRIC Determination

Compound

DETERMINATION

TABLE 1 of Antimony(II1) Compounds by Visual Titration

Molar ratio

Working range (mid

1. Antimony(II1)

oxide

1:l

5-30

2. Antimony(II1)

chloride

2: 1

840

3. Tartar emetic 4. Piperazine diantimonyl tartarate 5. Astiban (stibocaptatic)

2:l 1: 1

8-50 3-30

1:7

3-15

6. Anthiomaline

2:7

2-15

343

OF Sb(II1) COMPOUNDS Using DBH

% Found Methyl red

Methyl orange

99.8 (0.52) 99.3 (0.30) 99.7 100.2 (0.W 100.3 (0.34) 100.3 (0.4)

99.9 (0.37) 99.7 (0.57) 99.9 100.1 (0.70) 100.5 (0.49) 100.5 (0.52)

Amaranth

Indigotine

100.1 (0.40) 99.5

99.8 (0.35) 100.1 (0.5) 100.0 100.4 (0.5) 100.4 (0.75) 100.5

(0.6) 100.1 100.3 (0.45) 100.1 (0.82) 100.0 (0.57)

(0.6)

Note. The results are the averages of 12 separate determinations. The figures in parentheses are the coefficients of variation.

Potentiometric methods provide another approach to the detection of the endpoint. The DBH solution is added in increasing increments and the observed potential Q is plotted versus V (ml) of the titrant or, preferably, the first derivative curve (AE/AV) versus V is plotted to obtain sharp and more accurate endpoints as shown in Fig. 2. The molar ratios of the reaction of DBH with the antimony(III) compounds

Determination

of Antimony(II1)

TABLE 2 Compounds by Potentiometric and Spectrophotometric

Titrations

% Found Offld

Compound 1. Antimony(II1)

oxide

2. Antimony trichloride 3. Tartar emetic 4. Piperazine diantimonyl tartarate 5. Astiban 6. Anthiomaline

Potentiometry 99.7 (0.4) 99.5 (0.62) 99.8 (0.3) 100.5 (0.4) 100.5 (0.82) 100.1 (0.63)

Spectrophotometry 99.5 (0.52) 99.8 (0.32) 99.9 (0.4) 100.1 (0.29) 100.4 (0.85) 100.5 (0.32)

method 100.53 (13) (0.72) 100.1 (19) (0.69) 100.4 (18) (0.79) 100.9 (23) (1.15) 100.1 (13) (0.70) 99.8 (13)

(0.8)

Note. The results are the averages of six separate determinations. The figures in parentheses are the coefficients of variation.

BELAL,

IBRAHIM,

AND

EL-BUSHY

A(lcm)

+ io

1;

12 ml DBH

FIG. 1. Spectrophotometric

determination

of astiban (5 mg) with DBH (0.005 M) at 345 mn.

E(mV)

AEIAV 1800

looO-

900.

1600

8oQ-

1400

700.

1200

600-

1000

500.

800

400.

600

300.

400

200

ml DBH

FIG. 2. Potentiometric determination of tartar emetic (20 mg) with DBH (0.005 A4). (0) Normal titration curve; (0) first derivative curve.

BROMOMETRIC

DETERMINATION

OF

Sb(II1)

COMPOUNDS

345

346

BELAL,

IBBAHIM,

AND

EL-BBASHY

TABLE 3 Analysis of Dosage Forms Containing Antimony(II1) and Ollicial Methods Visual method

Preparation 1. Tartar emetic ampoule (120 mg antimony potassium tartaratekunpoule)

Spectrophotometric method

99.2 (0.62)

2. Bilharcid ampoules (60 mg antimony piperazinyl tartarate/ampoule)

101.2 (0.9)

3. Anthiomaline ampoules (mercaptosuccinic acid antimonate hexalithium salt, 60 mghl)

100.1 (0.7)

4. Astiban vials (0.5 g stibocaptate hexasodium salt/vial)

100.7 (0.22)

Compounds by the Proposed Potentiometric method

Oflicial method

99.0 (0.72)

99.2 (0.25)

98.5 (20) (0.51)

102.0 (0.95)

101.5 (0.75)

101.7 (13) (0.46)

100.2 (0.5)

99.8 (13) (0.7)

100.6 (0.85)

100.1 (13) (0.72)

100.4

(0.8)

Note. The results are the averages of six separate determinations. The figures in parentheses are the coefficients of variation. Preparations that are not official were analyzed using the published method (13).

studied are listed in Table 1. A proposal for the reaction pathway is presented in Scheme 1. Principally, the Br+ ion released from DBH in acid medium oxidizes the tervalent antimony to the pentavalent state: Sb(III)

+ Br+ + Sb(V) + Br-

As DBH produces two Br+ ions, the molar ratio of the reaction of DBH with antimony(II1) oxide and piperazine diantimonyl tartarate is 1: 1. Antimony(II1) chloride and tartar emetic (having only one antimony(II1) atom) react in the ratio of 2:l. Anthiomaline and astiban, on the other hand, react in the molar ratios of 2:7 and 1:7, respectively. In addition to the Sb(III), the sulfide groups are oxidized to the corresponding s&one. The reaction pathway is suggested in Scheme 1. The proposed method was applied to the determination of the studied compounds in dosage forms. The results obtained together with those from the offtcial methods (18, 19) are abridged in Table 3. Statistical analysis of the results using the Student t test and the F test (20) showed no significant difference between the performance of the two methods with regard to accuracy and precision. The proposed method is simple, rapid, and accurate. Various methods for the detection of the endpoint are available. The most striking feature of the proposed method is the stability of the reagent. Addition of 2% DMF allows the titrant to keep its titer for about 1 month and thus be suitable for routine analysis in control laboratories. CONCLUSION

A simple,

rapid,

and accurate titrimetric

method for the determination

of some

BROMOMETRIC

DETERMINATION

OF Sb(II1) COMPOUNDS

347

antimony(W) compounds and their dosageforms is described. In comparison with the offkial or published methods, the proposed method has the advantages of the stability of the titrant and the availability of various methods for the detection of the endpoint. Thus it is recommended for routine analysis in control laboratories. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20.

Bigois, M.; Marchand, M. Tulunta, 1972, 19, 157-161. Cotta-Ramusino, F.; Intonti, R. Metal. Ital., 1%7, 59, 645-649; C.A., 1968, 68, 799w. Schulte, K. F.; Henke, G.; Tjan, K. 2. Anal. Chem., 1970, 252, 358. Yamamato, M.; Urata, K.; Yamamato, Y. Anal. Lett., 1981, 14, 21-62. Huali, Y. Fen. Hsi. Hua Hsueh, 1981, 9, 75-77; A.A., 1981, 41, 3B, 164. Wilson, D. A.; Lewis, T. D. Analyst (London), 1963, 88, 585-589. Kolthoff, I. M.; Belcher, B. Volumetric Analysis, Vol. III, pp. 73, l%, 457, 513. Interscience, New York, 1976. Mody, N. F.; Desai, K. K.; Oza, B. N. J. Inst. Chem., 1976,48, 125. Rao, G. G.; Viswanath; Gwndikota, M. Anal. Chim. Acta, 1975, 79, 273. Fresno, C. D.; Valdes, I. Z. Anorg. Chem., 1929, 183, 251. Kiboku, M. Bunseki Kagaku, 1961, 10, 19-22. Zhdanov, A. K.; Kurochkina, N. A. Tr. Nauch Tashkentsh. Gas. Univ., 1964,264, 27-33; C.A., 1966, 65, 11,3318. Gawargious, Y. A.; Hassouna, M. E. M.; Hassan, H. E. A.; Habib, I. H. Pharmazie, 1980, 41, 59-60. Walash, M. I.; Rizk, M.; Abou-Ouf, A.; Belal, F. Analyst (London), 1983, 108, 626-632. Walash, M. I.; Rizk, M.; Abou-Ouf, A.; Belal, F. Anal. Lett., 1983, 16, 129148. Rizk, M.; Walash, M. I.; Abou-Ouf, A.; Belal, F. Anal. Lett., 1981, 14, 1407-1414. Belal, F.; Ibrahim, F.; El-Brashy, A. Analysf (London), 1988, 113, 637-639. The British Pharmncopoeia, H. M. Stationery Oflice, London, 1980. The British Pharmacopoeia, The Pharmaceutical Press, London, 1973. Sanders, D. H.; Murph, A. F.; Eng. R. J. Statistics, McGraw-Hill, New York, 1976.