Analysis of sulfonamides

ANALYSIS OF SULPHONAMIDES
12/15/20161 VIKAS COLLEGE OF PHARMACY
BY
@@@ Mr.S @@@
Pharmaceutical Analysis & Quality Assurance,
Vikas College Of Pharmacy,
Vissannapeta.

CONTENTS
12/15/20162
 INTRODUCTION
 CLASSIFICATION
 MECHANISM OF ACTION
 METHOD OF ANALYSIS
 CONCLUSION
 REFERENCES
VIKAS COLLEGE OF PHARMACY

Introduction
 Sulphonamide is derived from Prontosil,a prodrug that is
metabolised invivo by Azoreductase.
 Anti bacterial drugs used in the treatment of infections caused
by bacteria (gram positive and gram negative bacteria).
 Available in the form of tablets,
suspensions,parenterals,
opthalmic solutions,ointments.

Classification
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FOR
SYSTEMIC
INFECTIO
N
• Short acting
• Intermediate
acting
• Long acting
FOR
INTESTINAL
INFETIONS
• SULPHASALAZI
NE
• SULPHAGUANIDI
NE
TOPICAL
APPLICATION
• SULPHACETAMIDE
SODIUM
Sulphadiazin
e
Sulphathiazo
le
sulphamethoxaz
ole
sulphadoxi
ne

Structures of Sulphonamides

Mechanism of action
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 Sulfonamides (such as sulfamethoxazole) and diaminopyrimidines
(such as trimethoprim) inhibit different enzymes in the biosynthesis of
tetrahydrofolate in the bacteria.
 Due to the inhibited production of tetrahydrofolate, the bacteria is
unable to synthesize the thymidine, and is therefore also unable to
produce new DNA or RNA.
 This eventually leads to the death of the bacteria.

Mechanism of action

Analytical methods for sulfadrugs
Titrimetric method :
a)Diazotization titration
b)Nonaqueous titration
c)Argentometric titration
UV-spectrophotometry
Colorimetry
Chromatography
Fluorimetry 12/15/20168 VIKAS COLLEGE OF PHARMACY

SULPHADIAZINE
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 Chemical formula:C12H14N4O2S
 IUPAC name:4-amino-N-(4,6-
dimethylpyrimidin-2-yl)benzene-1-
sulfonamide
 Indication :For the treatment bacterial
infections causing bronchitis, prostatitis and
urinary tract infections.
 Do not take calcium, aluminium,
magnesium or iron supplements within 2
hours of taking this medication.

Diazotization
 When aromatic primary amines with nuclear –NH2 groups can be
determined quantitatively by standard sodium nitrite solution
required to convert them into diazonium salts.

SULPHATHIAZOLE
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 Chemical Formula
C9H9N3O2S2
 IUPAC Name 4-amino-N-
(1,3-thiazol-2-yl)benzene-1-
sulfonamide
 Indication: effective against a
wide range of gram positive
and gram negative
pathogenic microorganisms.
Although no longer used in
humans, it is used in cattle.

Non-Aqueous Titrations
 For determination of weak acids and weak bases
 TYPES
a. Acidimetry in non –aqueous titration
b. Alkalimetry in non –aqueous titration
 The sulfonamides contain weak acid group, so we are using
alkalimetry in NAT.
In these titration:
 Titrants used :Sodium methoxide,potassium methoxide,Lithium
methoxide.

 Solvents:
a. Strong base solvents: n-butyl amine ,Morpholine
b. Weak base solvents: DMF,Anhydrous pyridine
 Indicators:
1. 0.1N Alkali Methoxide Indicator
2. Thymol Blue Indicator
REAGENTS:
1. 0.1N alkali methoxide.Ex:CH3ONa:
12/15/201613
40ml of
methanol+50ml of
toulene in a dry flask
Add the sodium
metal
completely dissolve
add absolute
methanol+add50ml
of toulene
Alternatively add
methanol and
toulene to get one
litre of solution

ASSAY PROCEDURE
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Weigh 20 tablets
and grind it
1-2 mg of
sulphathiozole+25ml
DMF
Add 2 drops thymol
blue
Titrate with sodium
methoxide
Blue colur(End point)Perform the blank
0.3g of
thymol
blue
100ml of
absolute
methanol
Thymol
blue
indicator
2. Thymol blue indicator

Argentometric Titration
PRINCIPLE:
• Argentometric titration is otherwise
known as Precipitation titration
• Argentometry involves the use of the
standard solution of silver nitrate as
the titrant for estimation of the
halides(chlorides,bromides & iodides)

PROCEDURE
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Take 0.2-0.3g of
sulfonamides
Dissolve in 0.1 N
NaOH
solution is adjusted
to give blue colour
withThymophthalin
Volume make upto
50ml with distilled
water
Add 0.1 n H2SO4
to discharge blue
colour
Add 25ml of 0.1N
AgNO3
Whole
mixture is
allowed to
stand in dark
The ppt is
collected on
double fold
filter paper
Wash ppt
with water
Filterate is
acidifed
with HNO3
Excess AgNO3
is titrated with
0.1N Ammonium
thiocyanate
Using
ferric
alum
indicator

SULPHAMETHAZINE
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 Chemical Formula: C12H14N4O2S
 IUPAC Name: 4-amino-N-(4,6-
dimethylpyrimidin-2-yl)benzene-1-
sulfonamide
 Indication:For the treatment bacterial
infections causing bronchitis, prostatitis
and urinary tract infections.

UV-Spectrophotometry
Estimation of sulfamethazine:
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Take
sulfamethazine
sample
dissolved in
dil.H2SO4
Add small
amount of
resorcinol
Absorbance
measure at
λmax 320 nm.

12/15/201619
 Unknown should be compared with standard of same
concentration as the system obeys Beer’s law.
 Absorbance measured at 545nm.
 Sulfonamide(mg)=Absorbane of sample × standard(mg)
absorbance of standard

Colorimetry
12/15/201620
Analysis of sulfa drugs is
done by converting primary
amino group of
sulfonamides into a
diazonium salt by
diazotisation and later
coupling with suitable
chromogenic agent to form
Azo dye.
Automated Colorimetry

12/15/201621
Chromogenic Reagents
1.Para dimethyl amino benzaldehyde method
2.Diazotisation followed by coupling with BM Reagent
3.α-1,2-naphthaquinone-4-sulphonate sodium(folin’s reagent)
4.Thiobarbituric acid method
5.α-napthol method

PDAB (Para Dimethyl Amino Benzaldehyde) method
Drug solution is treated with solution of PDAB under acidic conditions results in
formation of AZOMETHINE,a yellow colour chromogen.
Measured at λmax :440nm.
It is an example of schiff”s base formation
22
R1=H
R2=C6H5-N(CH3)2
R3=C6H5SO2NH-R
YELLOW
SCHIFF’S
BASEPDAB
12/15/2016VIKAS COLLEGE OF PHARMACY

Diazotisation Followed By Coupling With BM Reagent
NH2SO2
DIAZONIUM SALT
N2⁺cl⁻
NHCHCHNH2
NHCH2CH2NH2
SO2NH
2
BM REAGENT
(N-1-NAPHTHYL-ETHYLENE
DIAMINE DIHYDRO CHLORIDE)
N=N
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PINK AZODYE

CHROMATOGRAPHIC METHOD
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• Paper chromatography is most
widely used for analysis of sulfa
drugs.
• The mobile phase used is a
mixture of equal volumes (1:1)
of 3%NH4OH and n-butanol.
PAPER CHROMATOGRAPHY
Paper Chromatography

12/15/201625
• Thin Layer Chromatography is
also most widely used for
analysis of sulfa drugs in
agricultural industries.
• Mobile phase is chloroform
and tert-butanol in ratio of
80:20
THIN LAYER CHROMATOGRAPHY
TLC plates

FLUORIMETRY
12/15/201626
Sulfa drug is diazotised with NaNO2
and form diazonium salt
Then it is coupled with
2,4,6Triaminopyridine.
The product obtained is subjected to
oxidation to produce triazo derivative
which has flouresence property and
can be analysed by spectro flourimeter
Fluorimeter

CONCLUSION
I here by conclude that there is a much
necessity for the study of analytical methods of
Sulphonamides as they are widely used class of
drugs as Anti bacterial agents……..

REFERENCES
• The Indian Pharmacopoeia1996
• P. D. Sethi, “Quantitative Analysis of Drugs in Pharmaceutical
Formulations”,.
• B. Morelli, J. Pharm. Biomed. Anal.,1989, 7, 577.
• P. B. Issopoulos, Acta. Pharm. Hung.,1992, 6, 3138.
• M. Knochen, J. Giglio and B.F. Reis, J. Pharm. Biomed. Anal., 2003, 33,
191.
• K.A Connors :Text book of Pharmaceutical Analysis,Third
edition,Page no:(62-63
• Higuchi,Beckmman&Hassan :Pharmaceutical Analysis,second
editiom,Page no:(137-157)
• V.N Rajasekharan,Text book of Pharmaceutical In Organic
Chemistry,Page no(126-128)

Analysis of sulfonamides

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