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Figure 3.2: Specimen chromatogram of blank solution
Figure 3.3: Specimen chromatogram of placebo solution
Figure 3.4: Specimen chromatogram of standard solution
Figure 3.5: Specimen chromatogram of sample solution
Figure 3.6: Specimen chromatogram of spiked impurities solution
Figure 3.7: Specimen chromatogram of spiked impurities and standard
Figure 3.8: Purity plot of unstressed sample solution
Figure 3.9: Purity plot of heat stressed sample solution
Figure 3.10: Purity plot of humidity stressed sample solution
Figure 3.11: Purity plot of sun light stressed sample solution
Figure 3.12: Purity plot of UV light stressed sample solution
Figure 3.13: Purity plot of acid stressed sample solution
Figure 3.14: Purity plot of base stressed sample solution
Figure 3.15: Purity plot of peroxide stressed sample solution
Figure 3.16: Purity plot of water stressed sample solution
Figure 4.2: The trial method chromatogram using mobile phase composition of buffer:
methanol: acetonitrile (89:8:3 v/v/v) respectively.
Fgure 4.3: The trial method system suitability chromatogram using increased flow rate of
0.5mL/ minute and decreased injection volume of 2µL.
Figure 4.4: The trial method system suitability chromatogram using sodium-1-heptane
sulphonate buffer and increased injection volume of 5µL.
Figure 4.5: The trial method system suitability chromatogram using sodium
buffer.
Figure 4.6: The trial method system suitability chromatogram using 0.8 mL / minute flow rate.
The trial method system suitability chromatogram using sodium-1-octane sulphonate
l method system suitability chromatogram using 0.8 mL / minute flow rate.
Figure 4.7: Chromatogram of blank
octane sulphonate
l method system suitability chromatogram using 0.8 mL / minute flow rate.
Figure 4.8: Chromatogram of placebo
Figure 4.9: Chromatogram of mesalamine standard solution
Figure 4.10: Chromatogram of mesalamine sample solution
Figure 4.11: Chromatogram of mesalamine system suitability solution
Figure 4.12: Chromatogram of mesalamine impurity mix solution
Figure 4.13: Chromatogram of mesalamine and impurity mix solution
Figure 4.14: Chromatogram of stressed mesalamine under visible light
Figure 4.15: Chromatogram of stressed mesalamine under UV light
Figure 4.16: Chromatogram of stressed mesalamine under heat
Figure 4.17: Chromatogram of stressed mesalamine under humidity
Figure 4.18(a): Chromatogram of stressed mesalamine under acid hydrolysis
Figure 4.18(b): Purity plot of stressed mesalamine under acid hydrolysis
Figure 4.19(a): Chromatogram of stressed mesalamine under base hydrolysis
Figure 4.19(b): Purity plot of stressed mesalamine under base hydrolysis
Figure 4.20: Chromatogram of stressed mesalamine under water
Figure 4.21: Chromatogram of stressed mesalamine under peroxide oxidation
Figure 5.3: Chromatograms of (a) blank solution and (b) placebo solution
Figure 5.4: Chromatogram of standard solution
Figure 5.5: Chromatogram of sample solution
Figure 5.6: The linearity graph of metformin
Figure 5.7: The linearity graph of vildagliptin
R² = 0.9999
200000
300000
400000
500000
600000
700000
800000
900000
1000000
1100000
1200000
2000 3000 4000 5000 6000 7000 8000Concentration (µg mL-1)
Met
form
in p
eak a
rea
(AU
) Metformin linearity graph
R² = 0.9999
50000
100000
150000
200000
250000
300000
350000
200 300 400 500 600 700 800
Vildagliptin linearity graph
Concentration (µg mL-1)
Vil
dag
lipti
n p
eak a
rea
(AU
)
Figure 6.2: Specimen chromatogram of blank solution
Figure 6.3: Specimen chromatogram of placebo solution
Figure 6.4: Specimen chromatograms of (a) standard and (b) sample solutions
Figure 7.2: Chromatogram of blank (diluent)
Figure 7.3: Chromatogram of placebo solution
Figure 7.4: Chromatogram of ciprofloxacin system suitability solution
Figure 7.5: Chromatogram of ciprofloxacin standard solution
Figure 7.6: Chromatogram of ciprofloxacin sample solution
ANALYTICAL CHROMATOGRAPHY STUDIES TO DEVELOP NOVEL METHODS FOR
EVALUATION OF
SRI KRISHNADEVARAYA UNIVERSITY, ANANTAPUR
In partial fulfillment for the Award of the degree of
ANATAPUR
ANALYTICAL CHROMATOGRAPHY STUDIES TO DEVELOP NOVEL METHODS FOR
EVALUATION OF PHARMACEUTICAL DRUG PRODUCTS
Thesis submitted to
SRI KRISHNADEVARAYA UNIVERSITY, ANANTAPURAMU
In partial fulfillment for the Award of the degree of
DOCTOR OF PHILOSOPHY
IN
CHEMISTRY
By
NANDIPATI SUBHAKAR
Under the Supervision of
Prof. V. KRISHNA REDDY
Department of Chemistry
SRI KRISHNADEVARAYA UNIVERSITY
ANATAPURAMU-515 003, ANDHRA PRADESH, INDIA
MARCH – 2014
ANALYTICAL CHROMATOGRAPHY STUDIES TO DEVELOP NOVEL METHODS FOR
PHARMACEUTICAL DRUG PRODUCTS
In partial fulfillment for the Award of the degree of
Prof. V. KRISHNA REDDY,
Department of Chemistry.
Residence : (08554) 273252
Mobile : 9490121379
E-Mail : [email protected]
This is to certify that the thesis entitled “
studies to develop novel methods for evaluation of pharmaceutical drug
products” is a bonafide research work done by
under my supervision in the department of chemistry, Sri Krishnadevaraya
University, Anantapuramu
Philosophy. The work embodied in this thesis is original
submitted in part or in full for the award of any degree or diploma by any
other University.
Date:
Place: Anantapuramu
CERTIFICATE
certify that the thesis entitled “Analytical chromatography
studies to develop novel methods for evaluation of pharmaceutical drug
is a bonafide research work done by Mr.Nandipati Subhakar,
under my supervision in the department of chemistry, Sri Krishnadevaraya
amu, for the award of the degree of Doctor of
Philosophy. The work embodied in this thesis is original and has not been
submitted in part or in full for the award of any degree or diploma by any
(Prof. V. KRISHNA REDDY)
Research Supervisor
SRI KRISHNADEVARAYA UNIVERSITY
ANANTAPURAMU – 515 003, ANDHRA PRADESH, INDIA
Analytical chromatography
studies to develop novel methods for evaluation of pharmaceutical drug
Nandipati Subhakar,
under my supervision in the department of chemistry, Sri Krishnadevaraya
, for the award of the degree of Doctor of
and has not been
submitted in part or in full for the award of any degree or diploma by any
(Prof. V. KRISHNA REDDY)
515 003, ANDHRA PRADESH, INDIA
DECLARATION
The work incorporated in this thesis entitled “Analytical chromatography
studies to develop novel methods for evaluation of pharmaceutical drug
products” has been carried out by me in the Department of Chemistry, Sri
Krishnadevaraya University, Anantapuramu, Andhra Pradesh, India. The
work embodied in this thesis is original and I declare that it has not been
submitted in part or in full for the award of any degree or diploma of any
other university.
Date: (NANDIPATI SUBHAKAR)
Place: Anantapuramu
ACKNOWLEDGMENTS
This thesis would have remained a distant dream had it not been for several wonderful
people. I would like to express my sincere gratitude to all of them.
First of all, I am extremely grateful to my adored research supervisor, Prof. V Krishna Reddy,
the retired Professor of Department of Chemistry, Sri Krishnadevaraya University, Anantapuramu,
for his valuable guidance, patience and consistent encouragement I received throughout the
research work. He is a person with an amicable and positive disposition; I consider it as a great
opportunity to do my doctoral program under his guidance.
I am sincerely thankful to Dr Reddy`s Laboratories Limited, Hyderabad, for providing moral
support in carrying out this research work along with professional services and I am highly thankful
to Sri Krishnadevaraya University, Anantapuramu, for giving an opportunity as a scholar, of the
university.
I am grateful to Prof. P Raveendra Reddy and Dr. P Venkata Ramana, for their advice during
the course of my thesis work.
I am thankful to Dr. Y Ramachandra Reddy, Mr.U Sreenivas and E SasikiranGoud for their
support and encouragement.Many friends have encouraged and helped me to achieve my goals. I
greatly value their friendship and I deeply appreciate their belief in me.
I owe my special gratitude to my beloved parents Sri N Chinna Rao and Smt. N Subhadra.
I have no suitable words that can fully describe their everlasting love for me. I am also thankful to
my brother Mr N Lakshminarayana and each individual of all my family members for their
affectionate encouragement extended to me throughout my career.
I owe my deepest gratitude towards my better half MrsN Bhanu Bhagyavathi, daughter N
Sahasra and son N Anunay, for their affection and support which enabled me to pursue my goal
whole heartedly.
CONTENTS
S. No Content Page No
Chapter - 1 Introduction to analytical techniques and drugs
Section –(i) : Introduction to analytical techniques 1 - 12
Section -(ii) : Introduction to drugs 13 - 33
Chapter - 2 Introduction to analytical method development and validation
Section -(i) : Introduction to analytical method development 34 - 60
Section –(ii) : Introduction to analytical method validation 60 - 80
Chapter - 3 Determination of omeprazole assay by UPLC 81 - 111
Chapter - 4 Determination of mesalamine assay by UPLC 112 - 141
Chapter - 5 Simultaneous estimation of vildagliptin and metformin by RP
– HPLC 142 - 167
Chapter - 6 Estimation of telmisartan by RP - HPLC 168 - 194
Chapter - 7 Determination of ciprofloxacin by UPLC 195 - 218