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Spectrophotometric determination of novalgin in tablets by use of potassium iodate
Talanra, Vol 36,No 8,pp 869-871,1989 Pnnted m Great Brrtam All nghts reserved
0039-9140/89 $3 OO+OOO
Copy&t 0 1989Maxwell Pergamon Macmrllanplc
SPECTROPHOTOMETRIC DETERMINATION OF NOVALGIN IN TABLETS BY USE OF POTASSIUM IODATE SAIDUL ZAFAR QURESHI, AHSAN SAEEDand TAUSIFUL HASAN Analyttcal Research Dtvtston, Department of Chemtstry, Ahgarh Mushm Umverstty, Ahgarh-202 002, India (Recemed 20 March 1987 Rewed
19 January 1989 Accepted 2 February 1989)
Summary-An mdmxt colour reaction has been studied for determmatton of novalgn m tablets The method IS simple, rapid and reproductble with a relative standard devtatton of 0 2% Novalgm IS determined spectrophotometrtcally by means of its colour reactton with potassium todate Beer’s law 1s obeyed over the range l-10 mg of drug. A tentative reaction mechanism has been proposed
Novalgm (analgm, dtpyrone) IS the sodium salt of (2,3 - dthydro - 1,5 - dtmethyl- 3 - 0x0 - 2 - phenyl - lH-
pyrazol-4-yl)ethylammomethane sulphomc aad It is a commonly used analgesic Its determination m tablets is, therefore, very Important. It has been determined m tablets and mJectlons by high-performance hqmd chromatography on a reversed-phase column, with ultravtolet detectton.’ Its spectrophotometric determmatton has been achieved by reaction with cermm(IV) and measurement of the resulting cermm(II1) wtth arsenazo III * Antipyrine and pyramidone can also be determined by this method. A coulometnc method for novalgin determmatton m tablets has also been reported.3 It has also been determined spectrophotometncally by reaction with N-bromosuccmimtde m acid media and measurement of the absorbance of the product at 290-450 nm.4 Anttpyrme and amidopyrme also give a positive reaction, A number of spectrophotometnc methods for novalgm and other analgesics have been reported based on use of potassmm ferrocyanide,5 sodmm nltnte,6 4-dtmethylammobenzaldehyde,’ Bromopheno1 Blue’ and potassium aurtchlonde9 as reagents In our studies, novalgm has been found to interact with potassmm iodate m presence of hydrochloric acid, to produce a yellowish red solutton Thts colour reactton has been studied for spectrophotometric determmation of the drug. EXPERIMENTAL Apparatus
A Bausch and Lomb Spectromc-20 was used for absorbance measurement Reagents
All chemicals used were of analyttcal grade A 0 5% w/v novalgm solutton was prepared m dtsttlled ethanol The tablets used were purchased locally A 0 1M potassium lodate solution and 1.OM hydrochloric acid were prepared with conductlvlty water
Procedure
To an ahquot of novalgm solution (contammg l-10 mg of the drug) m a 50-ml standard flask add 1 ml of O.lM potassium lodate followed by 1 ml of 1M hydrochlonc acid Let the reaction mixture stand for about 5 mm for the yellowish red colour to develop, then dilute to the mark with water Measure the absorbance at 460 nm against a reagent blank Procedure for analysrs of formulations
Stir a known weight of finely ground tablets or capsule contents (equivalent to 25 mg of novalgm) with 30 ml of distilled ethanol for 10 mm Filter off any residual sohd on a Whatman No 42 paper Make up the filtrate to volume m a 50-ml standard flask, then apply the procedure above
RESULTS A number of organic compounds were tested and tt was found that novalgm gives a characterrsttc yellowrsh red colour Many other drugs and a wide range of other compounds contanung different groups were found to gtve a negative test Those tested included the following Drugs etc Asptrm, codeme sulphate. oxyphenbutazone, propyphenazone, phenylbutazone, phenazone
sahcylate, phenacetin, caffeine, dtazepam rucotme and mcotmamtde could be tolerated m amounts up to 1 mg m determtnatton of 2 mg of novalgm Amzno-actds Htsttdme, aspartic acid, glutamtc acid, leucme, lysine, glycme, tryptophan, asparagme, argmme, L-alamne, fl-alanme and tyrosme. Acra!~ Acetic, formic, oxahc, citric, mahc, adtptc, proptomc, tartanc and pyruvic Sugars Glucose, fructose, rhamnose, sucrose, maltose, arabmose and xylose Aldehydes Acetaldehyde, benzaldehyde, crotonaldehyde and amsaldehyde. Ketones. Acetone, ethyl methyl ketone, diethyl ketone, methyl propyl ketone and cyclopentanone
869
870
SHORT
CO~NiCATiO~
Ammes. Ethyl, methyl, butyl, propyl, dlethyl and trtethyl Alcohols. Ethanol, methanol, propanol and butanoi Other compounds Acetamhde and vltamm B complex. Absorptmn spectrum The absorption spectrum of the reaction product 1s shown m Fig 1 The optimum wavelength is 460 nm Optrmum condltrons
350
/
/
/
440
520
600
Wavelength (nm)
Fig 1 Absorption spectrum of reaction product
Table I Dete~lnation
Drug and suppher 1 Baralgan (Hoechst)
2 Maxigestc (ETHICO)
3 Spasmizol (IDPL) 4 Ginox (Averest Chem Lab) 5 Promalgin (Uniloids)
6 Maxtgon (Unichem) 7 Algesin-0 (Alembic) 8 Spasmolysm (Std Pharm ) 9 Pamagm (Alkem) 10 Ultragin (Manner) 11 Zamalgm-A (Rallis) 12 Largesic (Lark Lab ) 13 Sedyn-A Forte (M M Labs) 14 Neogene (AFD) 15 Anadex (Concept) 16 Oxalgm (Cadila)
of nova&n
The absorbance of the product was found to be constant for up to 30 mm and then shghtly decreased With 5 0 mg of novalgm, absorbances of 0 O&0.14, 0.28, 0.31, 0 33, 0 33, 0 33 and 0 33 were obtained
(analgin) m pharma~utl~l rephcates)
preparations
Nommal composttion, mg 500 analgin 5 p-pipendmoethoxy-0-carbmethoxy benzophenone hydrochlortde 0 1 diphenylpiperidinoethyl acetamidebrom-0-methylate 250 analgin 100 oxyphenbutazone 2 5 diazepam 500 analgin 2 5 homatropme methyl bromide 10 phenobarbitone 500 analgin 100 ox~henbutazone 250 analgin 250 paracetamol 25 caffeine 500 analgin 5 p-piperidtn~thoxy-O-carbme~oxy benzophenone hydrochlorrde 300 analgin 100 oxyphenbutazone 500 analgin 10 dicyclomine hydrochlortde 500 analgin 5 diazepam 250 analgm 250 paracetamol 25 caffeine 250 analgm 15 caffeine 5 codeme phosphate 500 analgm 100 oxyphenbutazone 100 magnesium trisilicate 375 analgin 2 5 diazepam 20 diphenhydramine hydr~hlo~de 200 analgm 250 paracetamol 7 5 chlorpromazine hydrochloride 250 analgin 65 dextropropoxyphenhydr~~oride 500 analgm 100 oxyphenbutazone
(average and coefficient of variation, 5
Found by* present method, CV% mg 505 03
Found by comparison method,
mg
Reference for compartson method
509
18
244
06
504
01
498
18
510
03
515
18
264
05
495
04
499
18
293
07
298
18
514
01
520
18
459
05
-
256
06
257
18
255
08
258
17
474
02
-
-
324
01
-
-
250
02
253
18
249
02
259
17
535
04
531
17
-
871
SHORT COMMUNICATIONS
wtth 0 32, 0.34, 0.36, 0.40, 0 48, 0 50, 0.60 and 0.70 ml of 0.1 M potassium iodate. It IS clear from these data that 5.0 mg of novalgm needs at least 0.48 ml of 0 1M potassium iodate for reaction to be complete. However, the use of a larger volume does not affect the absorbance Therefore, 1 ml of O.lM potassium todate 1s recommended for the determination of novalgm. It was stmtlarly found that 1 ml of 1M hydrochloric acid is the opttmum volume. Conformity wzth Beer’s law Beer’s law holds good over the range l-10 mg of
towards todate The reaction occurs in acidic media and the rate depends on the concentratton of todate Cavazutti et al.” examtned the reacttvity of todtc acid with many classes of compounds of pharmaceuttcal interest, m order to estabhsh tts potential for detectmg and idenhfymg drugs separated by thm-layer chromatography on silica gel layers, since potassium iodate had already been used successfully for staining sympathomimettc ammes I6 On the basis of these studies, a tentative reaction mechanism is proposed Potassium todate interacts with the drug m presence of hydrochloric acid to liberate todme
HOsSCH, I
0 + 6KIOo + 6HCL
=
CHO I +2 SOIH
2
+ 4HCOOH
+ N,+
6KCl
+ 6 HI0 + 31,
I
novalgrn
novalgm The molar absorptrvity IS 0 1 x lo4 1 mole-’ cm-’ The correlation coefficient for cahbratton was 0.99 Ten replicate determmatrons of 2.0 mg of novalgn gave a standard devtatton of 3 pg (relative standard deviatton 0.2%) The mterference tests are described above. Applzcatlons The method was used to determine nova&n in vartous pharmaceuttcal preparattons. The results are shown m Table 1. None of the other ingredients of the samples reacts with either todme or iodate DISCUSSION
The methods for the determmation of various organic compounds by oxidation with potassium iodate have been dtscussed in greater detail elsewhere lo The iodine liberated during the course of reaction IS distilled off and determined. The oxidation reaction m acidic medium depends on both the substrate and the experimental conditions. Reaction IS favoured by the presence of hydrogen atoms bound to carbon atoms activated by a functional group.“-‘4 In particular, hydrogen atoms on aromatic nuclei wtth electron-donating substttuents are very reactive
The liberation of iodine IS shown by the productton of a blue colour with starch REFERENCES
1
N
H Eddme, F Bressolle, B Mandrou and H Fabre,
Analyst, 1982, 107, 67
F Buhl and U Hachula, Chem Anal Warsaw, 1981, 26, 395 3 N Kosta, V Ksenija and M MlrJana, Acta Pharm Jugosl, 1984, 34, 177 4 N V Pathak and I C Shukla, J Indran Chem Sot , 2
1983, 60, 206 P George, Indmn J Pharm , 1974, 36, 14 6 H Abdme, A S Sophl and G I Morcas Magdl, 5
Pharm Scl , 1973, 62, 1834 7
R Bontemps, J Parmentler and M Dlesse, J Pharm ,
8 9
D M Shmghal, Indran Drugs Pharm Ind, 1976, 11,31 N Shlrltsu and D Yakugakuku, Kenbyu Nomo, 1965, 13, 1 W Hurka, Mkrochemle, 1944, 31, 83 R J Wdhams, E Rohrman and B. E Chnstensen, J. Am Chem. Sot, 1937, 59, 281 J 0 Edwards, Chem Rev, 1952, 50, 461 R A Garrett, R J Glllesple and J B Semor, Inorg Chem , 1965, 4, 563 K Nabeslma, Okayama Igakkl Zassht, 1939,51, 1331 G Cavazzuttl, L Gaghavdl, A Amato, M Profih and V J Zagarese, J Chromatog, 1983, 263, 528 K Macek and I M Hais, m Handbuch der Papterchromatographle, G Fisher (ed ), Band I, Verlag-Jena, Jena, 1958 Pharmacopoeia of Indta, Vol I, p 44, 1985 L Vlktor, Acta Pharm Hung, 1971, 41, 51
1968, 23, 222
10 11 12 13 14 IS 16 17 18
0039-9140/89 $3 OO+OOO
Copy&t 0 1989Maxwell Pergamon Macmrllanplc
SPECTROPHOTOMETRIC DETERMINATION OF NOVALGIN IN TABLETS BY USE OF POTASSIUM IODATE SAIDUL ZAFAR QURESHI, AHSAN SAEEDand TAUSIFUL HASAN Analyttcal Research Dtvtston, Department of Chemtstry, Ahgarh Mushm Umverstty, Ahgarh-202 002, India (Recemed 20 March 1987 Rewed
19 January 1989 Accepted 2 February 1989)
Summary-An mdmxt colour reaction has been studied for determmatton of novalgn m tablets The method IS simple, rapid and reproductble with a relative standard devtatton of 0 2% Novalgm IS determined spectrophotometrtcally by means of its colour reactton with potassium todate Beer’s law 1s obeyed over the range l-10 mg of drug. A tentative reaction mechanism has been proposed
Novalgm (analgm, dtpyrone) IS the sodium salt of (2,3 - dthydro - 1,5 - dtmethyl- 3 - 0x0 - 2 - phenyl - lH-
pyrazol-4-yl)ethylammomethane sulphomc aad It is a commonly used analgesic Its determination m tablets is, therefore, very Important. It has been determined m tablets and mJectlons by high-performance hqmd chromatography on a reversed-phase column, with ultravtolet detectton.’ Its spectrophotometric determmatton has been achieved by reaction with cermm(IV) and measurement of the resulting cermm(II1) wtth arsenazo III * Antipyrine and pyramidone can also be determined by this method. A coulometnc method for novalgin determmatton m tablets has also been reported.3 It has also been determined spectrophotometncally by reaction with N-bromosuccmimtde m acid media and measurement of the absorbance of the product at 290-450 nm.4 Anttpyrme and amidopyrme also give a positive reaction, A number of spectrophotometnc methods for novalgm and other analgesics have been reported based on use of potassmm ferrocyanide,5 sodmm nltnte,6 4-dtmethylammobenzaldehyde,’ Bromopheno1 Blue’ and potassium aurtchlonde9 as reagents In our studies, novalgm has been found to interact with potassmm iodate m presence of hydrochloric acid, to produce a yellowish red solutton Thts colour reactton has been studied for spectrophotometric determmation of the drug. EXPERIMENTAL Apparatus
A Bausch and Lomb Spectromc-20 was used for absorbance measurement Reagents
All chemicals used were of analyttcal grade A 0 5% w/v novalgm solutton was prepared m dtsttlled ethanol The tablets used were purchased locally A 0 1M potassium lodate solution and 1.OM hydrochloric acid were prepared with conductlvlty water
Procedure
To an ahquot of novalgm solution (contammg l-10 mg of the drug) m a 50-ml standard flask add 1 ml of O.lM potassium lodate followed by 1 ml of 1M hydrochlonc acid Let the reaction mixture stand for about 5 mm for the yellowish red colour to develop, then dilute to the mark with water Measure the absorbance at 460 nm against a reagent blank Procedure for analysrs of formulations
Stir a known weight of finely ground tablets or capsule contents (equivalent to 25 mg of novalgm) with 30 ml of distilled ethanol for 10 mm Filter off any residual sohd on a Whatman No 42 paper Make up the filtrate to volume m a 50-ml standard flask, then apply the procedure above
RESULTS A number of organic compounds were tested and tt was found that novalgm gives a characterrsttc yellowrsh red colour Many other drugs and a wide range of other compounds contanung different groups were found to gtve a negative test Those tested included the following Drugs etc Asptrm, codeme sulphate. oxyphenbutazone, propyphenazone, phenylbutazone, phenazone
sahcylate, phenacetin, caffeine, dtazepam rucotme and mcotmamtde could be tolerated m amounts up to 1 mg m determtnatton of 2 mg of novalgm Amzno-actds Htsttdme, aspartic acid, glutamtc acid, leucme, lysine, glycme, tryptophan, asparagme, argmme, L-alamne, fl-alanme and tyrosme. Acra!~ Acetic, formic, oxahc, citric, mahc, adtptc, proptomc, tartanc and pyruvic Sugars Glucose, fructose, rhamnose, sucrose, maltose, arabmose and xylose Aldehydes Acetaldehyde, benzaldehyde, crotonaldehyde and amsaldehyde. Ketones. Acetone, ethyl methyl ketone, diethyl ketone, methyl propyl ketone and cyclopentanone
869
870
SHORT
CO~NiCATiO~
Ammes. Ethyl, methyl, butyl, propyl, dlethyl and trtethyl Alcohols. Ethanol, methanol, propanol and butanoi Other compounds Acetamhde and vltamm B complex. Absorptmn spectrum The absorption spectrum of the reaction product 1s shown m Fig 1 The optimum wavelength is 460 nm Optrmum condltrons
350
/
/
/
440
520
600
Wavelength (nm)
Fig 1 Absorption spectrum of reaction product
Table I Dete~lnation
Drug and suppher 1 Baralgan (Hoechst)
2 Maxigestc (ETHICO)
3 Spasmizol (IDPL) 4 Ginox (Averest Chem Lab) 5 Promalgin (Uniloids)
6 Maxtgon (Unichem) 7 Algesin-0 (Alembic) 8 Spasmolysm (Std Pharm ) 9 Pamagm (Alkem) 10 Ultragin (Manner) 11 Zamalgm-A (Rallis) 12 Largesic (Lark Lab ) 13 Sedyn-A Forte (M M Labs) 14 Neogene (AFD) 15 Anadex (Concept) 16 Oxalgm (Cadila)
of nova&n
The absorbance of the product was found to be constant for up to 30 mm and then shghtly decreased With 5 0 mg of novalgm, absorbances of 0 O&0.14, 0.28, 0.31, 0 33, 0 33, 0 33 and 0 33 were obtained
(analgin) m pharma~utl~l rephcates)
preparations
Nommal composttion, mg 500 analgin 5 p-pipendmoethoxy-0-carbmethoxy benzophenone hydrochlortde 0 1 diphenylpiperidinoethyl acetamidebrom-0-methylate 250 analgin 100 oxyphenbutazone 2 5 diazepam 500 analgin 2 5 homatropme methyl bromide 10 phenobarbitone 500 analgin 100 ox~henbutazone 250 analgin 250 paracetamol 25 caffeine 500 analgin 5 p-piperidtn~thoxy-O-carbme~oxy benzophenone hydrochlorrde 300 analgin 100 oxyphenbutazone 500 analgin 10 dicyclomine hydrochlortde 500 analgin 5 diazepam 250 analgm 250 paracetamol 25 caffeine 250 analgm 15 caffeine 5 codeme phosphate 500 analgm 100 oxyphenbutazone 100 magnesium trisilicate 375 analgin 2 5 diazepam 20 diphenhydramine hydr~hlo~de 200 analgm 250 paracetamol 7 5 chlorpromazine hydrochloride 250 analgin 65 dextropropoxyphenhydr~~oride 500 analgm 100 oxyphenbutazone
(average and coefficient of variation, 5
Found by* present method, CV% mg 505 03
Found by comparison method,
mg
Reference for compartson method
509
18
244
06
504
01
498
18
510
03
515
18
264
05
495
04
499
18
293
07
298
18
514
01
520
18
459
05
-
256
06
257
18
255
08
258
17
474
02
-
-
324
01
-
-
250
02
253
18
249
02
259
17
535
04
531
17
-
871
SHORT COMMUNICATIONS
wtth 0 32, 0.34, 0.36, 0.40, 0 48, 0 50, 0.60 and 0.70 ml of 0.1 M potassium iodate. It IS clear from these data that 5.0 mg of novalgm needs at least 0.48 ml of 0 1M potassium iodate for reaction to be complete. However, the use of a larger volume does not affect the absorbance Therefore, 1 ml of O.lM potassium todate 1s recommended for the determination of novalgm. It was stmtlarly found that 1 ml of 1M hydrochloric acid is the opttmum volume. Conformity wzth Beer’s law Beer’s law holds good over the range l-10 mg of
towards todate The reaction occurs in acidic media and the rate depends on the concentratton of todate Cavazutti et al.” examtned the reacttvity of todtc acid with many classes of compounds of pharmaceuttcal interest, m order to estabhsh tts potential for detectmg and idenhfymg drugs separated by thm-layer chromatography on silica gel layers, since potassium iodate had already been used successfully for staining sympathomimettc ammes I6 On the basis of these studies, a tentative reaction mechanism is proposed Potassium todate interacts with the drug m presence of hydrochloric acid to liberate todme
HOsSCH, I
0 + 6KIOo + 6HCL
=
CHO I +2 SOIH
2
+ 4HCOOH
+ N,+
6KCl
+ 6 HI0 + 31,
I
novalgrn
novalgm The molar absorptrvity IS 0 1 x lo4 1 mole-’ cm-’ The correlation coefficient for cahbratton was 0.99 Ten replicate determmatrons of 2.0 mg of novalgn gave a standard devtatton of 3 pg (relative standard deviatton 0.2%) The mterference tests are described above. Applzcatlons The method was used to determine nova&n in vartous pharmaceuttcal preparattons. The results are shown m Table 1. None of the other ingredients of the samples reacts with either todme or iodate DISCUSSION
The methods for the determmation of various organic compounds by oxidation with potassium iodate have been dtscussed in greater detail elsewhere lo The iodine liberated during the course of reaction IS distilled off and determined. The oxidation reaction m acidic medium depends on both the substrate and the experimental conditions. Reaction IS favoured by the presence of hydrogen atoms bound to carbon atoms activated by a functional group.“-‘4 In particular, hydrogen atoms on aromatic nuclei wtth electron-donating substttuents are very reactive
The liberation of iodine IS shown by the productton of a blue colour with starch REFERENCES
1
N
H Eddme, F Bressolle, B Mandrou and H Fabre,
Analyst, 1982, 107, 67
F Buhl and U Hachula, Chem Anal Warsaw, 1981, 26, 395 3 N Kosta, V Ksenija and M MlrJana, Acta Pharm Jugosl, 1984, 34, 177 4 N V Pathak and I C Shukla, J Indran Chem Sot , 2
1983, 60, 206 P George, Indmn J Pharm , 1974, 36, 14 6 H Abdme, A S Sophl and G I Morcas Magdl, 5
Pharm Scl , 1973, 62, 1834 7
R Bontemps, J Parmentler and M Dlesse, J Pharm ,
8 9
D M Shmghal, Indran Drugs Pharm Ind, 1976, 11,31 N Shlrltsu and D Yakugakuku, Kenbyu Nomo, 1965, 13, 1 W Hurka, Mkrochemle, 1944, 31, 83 R J Wdhams, E Rohrman and B. E Chnstensen, J. Am Chem. Sot, 1937, 59, 281 J 0 Edwards, Chem Rev, 1952, 50, 461 R A Garrett, R J Glllesple and J B Semor, Inorg Chem , 1965, 4, 563 K Nabeslma, Okayama Igakkl Zassht, 1939,51, 1331 G Cavazzuttl, L Gaghavdl, A Amato, M Profih and V J Zagarese, J Chromatog, 1983, 263, 528 K Macek and I M Hais, m Handbuch der Papterchromatographle, G Fisher (ed ), Band I, Verlag-Jena, Jena, 1958 Pharmacopoeia of Indta, Vol I, p 44, 1985 L Vlktor, Acta Pharm Hung, 1971, 41, 51
1968, 23, 222
10 11 12 13 14 IS 16 17 18