STABILITY INDICATING HPLC METHOD FOR DETERMINATION OF...

Vol. 5 | No.1 | 90-105 | January-March | 2012

ISSN: 0974-1496 | CODEN: RJCABP

http://www.rasayanjournal.com

MARAVIROC AND ITS DEGRADANTS/IMPURITIES V.Kalyana Chakravarthy and D.Gowri Sankar

STABILITY INDICATING HPLC METHOD FOR

DETERMINATION OF MARAVIROC AND ITS

DEGRADANTS/IMPURITIES IN BULK AND

PHARMACEUTICAL FORMULATION

V.Kalyana Chakravarthy* and D.Gowri Sankar College of Pharmaceutical Sciences, Andhra University, Visakhapatnam-530 003, India.

*E-mail: Kalyan224@rediffmail

ABSTRACT A reverse phase liquid chromatography (RP-LC) method has been developed and subsequently validated for the

determination of Maraviroc and its intermediates in bulk and pharmaceutical formulation. Seperation was achieved

in Gradient mode with a X-Bridge C18 (Make: Waters (US); 250 mmx4.6 mm I.D; particle size 5 µm) column with

Mobile phase A (1.36 g of Potassium dihydrogen orthophosphate buffer and 1.0mL of orthophosphoric acid in

1000mL of water) and Mobile phase B (Methanol and Mobile phase-A in the ratio of 700:300 v/v respectively). The

flow rate was 0.8mL/minute, column temperature was 45°C and the run time was 70minutes. UV detection was

performed at 210nm and the sample temperature was maintained at Ambient. The injection volume is 20µL. The

method is simple, rapid, selective and stability indicating. The described method of Maraviroc is linear over a range

of 0.0989 µg/mL to 3.9561 µg/mL. The method precision for the determination of Related Substances was below

2.0%RSD. Limit of Detection (LOD) and Limit of Quantification (LOQ) of all related impurities of Maraviroc was

established and ranged from 0.0241 µg/mL to 0.1521 µg/mL for LOD and 0.0485 µg/mL to 0.3972 µg/mL for LOQ.

The method is useful in the quality control of Bulk manufacturing and also in pharmaceutical formulations.

Keywords: LC Determination, Maraviroc, Maraviroc Impurities. © 2012 RASĀYAN. All rights reserved.

INTRODUCTION Maraviroc is an entry inhibitor and works by blocking HIV from entering human cells. Specifically

maraviroc is a selective, slowly reversible, small molecule antagonist of the interaction between human

CCR5 and HIV-1 gp120. Maraviroc selectively binds to the human chemokine receptor CCR5 present on

the membrane of CD4 cells (T-cells), preventing the interaction of HIV-1 gp120 and CCR5 necessary for

CCR5-tropic HIV-1 to enter cells. Maraviroc has the chemical name 4,4-difluoro-N-[(1S)-3-[(1R,5S)-3-

[3-methyl-5-(propan-2-yl)-4H-1,2,4-triazol-4-yl]-8-azabicyclo[3.2.1]octan-8-yl]-1-

phenylpropyl]cyclohexane-1-carboxamide Maraviroc is a white to yellowish or brownish powder with a

molecular formula of C29H41F2N5O and a molecular weight of 513.67. Maraviroc is practically insoluble

in water, slightly soluble in ethanol, Soluble in Methanol, Dimethyl sulfoxide and PEG 400. Its Chemical

structure is given below1-2

(Figure-1).

Fig.-1: Maraviroc


Maraviroc and Its Degradants/Impurities V.Kalyana Chakravarthy and D.Gowri Sankar 91

It is not official in any pharmacopoeia, few liquid chromatography procedures have been reported for the

determination of Maraviroc and its Related Impurities3-4

.The author have developed a liquid

chromatographic method which would serve as a rapid and reliable method for the determination of

Maraviroc and its Related Impurities in Bulk and pharmaceutical dosage forms.

Maraviroc Impurity-A

Maraviroc Impurity-B

Fig.-2: Maraviroc related impurities

EXPERIMENTAL5-7

Instrumentation

The analysis of the drug was carried out on a Waters LC system equipped with 2695pump, 2996

photodiode array detector was used and a Reverse phase HPLC column X-Bridge C18 (Make: Waters

(US) ; 250 mm x 4.6 mm I.D; particle size 5 µm) was used. The output of signal was monitored and

integrated using waters Empower 2 software.

Chemicals and solvents

Methanol (HPLC Gradient Grade), Orthophosphoric acid (HPLC Grade) and Potassium

dihydrogen Orthophosphate of GR Grade were obtained from E. Merck (India) Ltd., Mumbai and HPLC

Grade water from Millipore.

Solutions

Buffer preparation Accurately weigh and transfer about 1.36 g of Potassium dihydrogen orthophosphate in 1000 mL

of purified water and add 1.0 mL of orthophosphoric acid and mix.



Mobile phase preparation-A

Use Buffer preparation as mobile phase-A. Filter through 0.45µm membrane filter and degas.

Mobile phase preparation-B

Use filtered (0.45µm membrane filter) and degassed mixture of Methanol and Mobile phase-A in the ratio

of 700:300 v/v respectively.

Diluent preparation

Add 2.0 mL of Orthophosphoric acid in to a 1000 mL of purified water and mix well.

Preparation of Diluted Standard preparation Accurately weigh and transfer about 25.0mg of Maraviroc working standard into a 250 mL volumetric

flask, add about 15 mL of Methanol, sonicate to dissolve and dilute to volume with diluent.

Transfer 2.0 mL of the above solution into a 100 mL volumetric flask and dilute to volume with diluent.

Sample preparation Accurately weigh and finely powder not fewer than 20 tablets, and transfer the powder equivalent

to 250 mg of Maraviroc into a 250 mL volumetric flask. To this added 15 mL of Methanol sonicate for 15

minutes and add about 160 mL of diluent, sonicate for 15minutes with occasional shaking. Cool the

solution to room temperature and dilute to volume with diluent and mix. Centrifuge the solution at 3000

RPM for 15 minutes.

Transfer the supernatant solution into HPLC Vial and inject on to the HPLC System.

Impurity Stock Preparation Accurately weigh and transfer about 5.0mg of Impurity A and 5.0mg of Impurity B into a 100 mL

volumetric flask add 30 mL of Methanol sonicate to dissolve and dilute to volume with diluent.

Peak Identification Solution Accurately weigh and transfer about 50.0mg of Maraviroc working standard into a 50 mL

volumetric flask and add about 30 mL of diluent and sonicate to dissolve. Transfer 2.0 mL of Impurity

Stock Solution and dilute to volume with diluent.

Chromatographic conditions X-Bridge C18 (Make: Waters (US)); 250 mmx4.6 mm I.D; particle size 5 µm)) was used for

analysis at column temperature 45°C. The mobile phase was pumped through the column at a flow rate of

0.8mL/min. The sample injection volume was 20 µL and the sample temperature was maintained at

Ambient. The photodiode array detector was set to a wavelength of UV-210nm for Maraviroc and its

related impurities and Chromatographic Gradient programme (Table-1) runtime was 70minutes.

Preparation of Degradation samples for Specificity Study

For Acid degradation Maraviroc sample was refluxed with 5N HCl at 60°C for 1hour and then neutralized by adjusting

pH to 7.0 with 5N NaOH. The Solution was further diluted to required concentration with diluent.

Note: Sample was not degraded in 0.1N HCL and 1N HCL. So high stress conditions 5N HCL was used.

For Base degradation

Maraviroc sample was refluxed with 2N NaOH at 60°C for 1hour and then neutralized by

adjusting pH to 7.0 with 2N HCl. The Solution was further diluted to required concentration with diluent.

Note: Sample was not degraded in 0.1N NaOH and 1N NaOH. So high stress conditions 2N NaOH was

used.

For Oxidative degradation Maraviroc sample was refluxed with 30%H2O2 by heating on water bath at 60°C for 1hour. The

Solution was further diluted to required concentration with diluent.

For Photolytic degradation Maraviroc sample was exposed to UV (200watt hour/m

2) and Visible (1.2million Lux hours) as

per ICH Guidelines. The Sample was prepared as per sample preparation.



For Thermal Degradation Maraviroc sample was exposed to Temperatures at 105°C for 3days. The Sample was prepared as

per sample preparation.

For Water Degradation

Maraviroc sample was refluxed with water by heating on water bath at 100°C for 1hour. The

Sample was prepared as per sample preparation.

For Humidity Degradation Maraviroc sample was exposed to 85% Humidity (Prepared potassium nitrate saturated solution)

at 3days. The Sample was prepared as per sample preparation.

RESULTS AND DISCUSSION Method development

5-7

To develop a suitable and robust LC method for the determination of Maraviroc and its related impurities,

different mobile phases, columns and Gradient programmes were employed to achieve the best separation

and resolution. The method development was started with Inertsil ODS 3V ((Make: GL Sciences (Japan);

250 mmx4.6 mm I.D; particle size 5 µm)) which gives best resolution between Maraviroc and its

impurities. Separation was achieved with Mobile phase A (1.0 mL Orthophosphoric acid into a 1000 mL

of purified water and mix well). Filter the solution through 0.45µm membrane filter. Mobile phase B

containing Methanol as eluent with flow rate of 1.5 mL /minute and the gradient conditions refer (Table-

2).

The injection volume was 20 µL, column temperature was 35°C and the sample temperature was

Ambient. UV detection was performed at 210nm for Maraviroc impurities and Known impurity

Maraviroc impurity B. Maraviroc impurity A is estimated at 205nm. In this trial blank peaks observed at

retention time of Maraviroc and its known impurities A & B. So method needs to be optimized. In the

second trial mobile phase and chromatographic conditions are same except HPLC Column. The column

used in this trial was Develosil ODS MG5 ((Make: Nomura chemicals (Japan); 250 mmx4.6 mm I.D;

particle size 5 µm)). In this trial also blank peaks observed at retention time of Maraviroc and its known

impurities A & B. So method needs to be optimized. In trial 3 the following chromatographic conditions

was used to separate Maraviroc and its related impurities. Mobile phase A (1.36 g of Potassium

dihydrogen orthophosphate buffer and 1.0mL of orthophosphoric acid in 1000mL of water) and Mobile

phase B (Methanol and mobile phase-A in the ratio of 700:300 v/v respectively). The injection volume

was 20 µL, the column temperature was 40°C and the sample temperature was Ambient. UV detection

was performed at 210nm. The Diluent used for sample preparation was 2.0 mL of Orthophosphoric acid

in to 1000 mL of purified water. The column used in this trial was Develosil ODS HG5 ((Make: Nomura

chemicals (Japan); 250 mmx4.6 mm I.D; particle size 5 µm)) and the gradient conditions refer (Table -3).

In the above trial Placebo peaks are merging with known impurities. So the method needs to be

optimized. In the final trial Chromatographic conditions, mobile phase and diluent are same as per trial 3

except the column. X-Bridge C18 (Make: Waters (US); 250 mm x 4.6 mm I.D; particle size 5 µm) was

used for analysis for Maraviroc and its related impurities, runtime was 70minutes and for the gradient

conditions refer (Table-1).

All the impurities are well separated from each other and with Maraviroc peak. Established

Relative response factors for all known impurities reported and reported in Table5 and the spectrums are

given in [Fig-3]. Prepared not less than seven preparations containing mixture of Drug substance and

Impurities in the concentration range of 0.1 % to 1.0 % (eg... 0.1%, 0.2%, 0.3%, 0.5%, 0.7%, 0.8% and

1.0%) with respect to test concentration for establishing RRF. Weighed and transferred 4.97mg of

Maraviroc, 5.03mg of Maraviroc Impurity A and 5.04mg of Maraviroc impurity B into a 100ml

volumetric flask added 20mL of Methanol sonicate to dissolve and made the volume with diluent and

established RRF by slope method with above concentration range. The retention time of Maraviroc was

37.7 minutes and the peak shape was good. The chromatogram of Maraviroc standard using the proposed

RS method is shown in [Fig-4] and System suitability results of the method for Related Substances are



presented in Table-4. For relative response factors and relative retention times of (Refer Table-5)

Maraviroc and its known impurities shows a significant UV absorbance at Wavelength 210nm. Hence this

wavelength was selected for detection for the analysis of Maraviroc and its related impurities. Based on

the better peak shape of the Maraviroc and its related impurities X-Bridge C18 (Make: Waters (US) ; 250

mm x 4.6 mm I.D; particle size 5 µm) column was selected as a suitable column.

Method validation5-7

The developed LC method validated for Maraviroc and its related Substances by using the following

parameters.

Specificity

Blank and Placebo interference A study was performed to establish the placebo interference. Related substances analysis was

performed on placebo sample in triplicate preparations by taking equivalent weight of the placebo in

portion of test preparation as per test method. Chromatograms of Blank and Placebo solutions showed no

peaks at the retention time of Maraviroc peak and its related impurities. This indicates that the excipients

used in the formulation do not interfere in estimation of Maraviroc in Maraviroc Tablets. The

chromatogram of Maraviroc and its related impurities A, B, Blank and Placebo, diluted standard of

Maraviroc, spiked and Unspiked sample using the proposed method is shown in [Fig-4 to Fig-10].

Interference from degradation products

A study was conducted to demonstrate the effective separation of degradants from Maraviroc and

its related known impurities. Separate portions of Drug product, Drug substance and Placebo were

exposed to the stress conditions to induce degradation. Stressed samples were injected into the HPLC

system with photo diode array detector as per following test method conditions. All degradant peaks were

resolved from Maraviroc peak and its related impurities in the chromatograms of all samples. The

Chromatograms of the stressed samples were evaluated for peak purity of Maraviroc using Empower2

software. In all forced degradation samples, peak purity was passed for Maraviroc and its related

impurities. Maraviroc peak Purity angle is less than purity threshold. The results are given Table-6. The

method can be used for determining Maraviroc and its related impurities in bulk and pharmaceutical

formulations. The chromatograms of degradation study was shown in [Fig- 4 to Fig-17].

Limit of Detection and Limit of Quantification A study to establish the Limit of detection and Limit of Quantification of Maraviroc and its

related known impurities were conducted. Limit of detection and Limit of Quantification were established

based on signal to noise ratio. A series of solutions with Maraviroc and its related impurities were

injected. Limit of detection for related impurities were established by identifying the concentration which

gives signal to noise ratio about 3. Limit of quantification was established by identifying the

concentration which gives signal to noise ratio about 10.

Precision of Maraviroc related impurities at about Limit of Quantitation were conducted. Six test

preparations of Maraviroc tablets having related impurities at about Limit of quantitation was prepared

and injected into the HPLC system. The %RSD at LOQ level was calculated for all known impurities and

found to be less than 5.0%.

Accuracy of Maraviroc related impurities at about Limit of Quantitation was conducted. Test solutions

spiked with related impurities at about Limit of Quantitation was prepared in triplicate and injected into

HPLC system and calculated the % recovery. The mean recovery of Maraviroc related impurities at about

Limit of Quantitation was ranged from 98.5% to 99.3%. The results are given under Table-7.

Linearity of detector response

Maraviroc and its Related Impurities Linearity of detector response of all known Maraviroc and its related impurities is established by

plotting a graph to concentration versus area of Maraviroc related impurities A and B and determining the

correlation coefficient. A series of solutions of Maraviroc and its related impurities in the concentration

ranging from Limit of Quantitation level to 200% of target concentration were prepared and injected into



the HPLC System. Linearity results of the method are presented in Table-8 to Table-10 and Linearity

graphs was shown in [Fig- 18 to Fig-20].

Precision of test Method The precision of test method of all known impurities of Maraviroc was evaluated by spiking all

known impurities at target concentration level (0.2%) on Tablets. The Relative standard deviations of all

known impurities were calculated and found to be less than 5.0%. The results were given in Table-11.

Accuracy

A study of recovery of Maraviroc related impurities in spiked samples of Maraviroc test

preparation was conducted. Samples were prepared in triplicate by spiking of all known impurities in test

preparation at 50%, 100%, 150% and 200% of the target concentration level of Maraviroc known

impurities.The average %recovery of Maraviroc related impurities was calculated and given in Table-12.

Maraviroc related impurities from spiked were found to be in the range of 98.4 to 100.6%.

Ruggedness A study to establish the stability of Maraviroc and its related impurities in standard and test

solutions were conducted on bench top and refrigerator at Initial, 1 day and 2 day. The assays of

Maraviroc in standard and test solutions were estimated against freshly prepared standard each time. The

difference in% assay of standard and test solutions from initial to 1 day and 2 days was calculated and

given in Table-13 & Table-14. From the above study, it was established that the Standard and sample

preparations are stable for a period of 48hours at room temperature (25°C±2°C) and at refrigerator

condition (2°C-8°C).

Robustness

A study to establish the effect of variation in mobile phase composition, Flow, temperature and

pH of Buffer in mobile phase was conducted. Standard and test solution

Spiked with known related impurities of Maraviroc prepared as per proposed method were injected into

HPLC system. The system suitability parameters, % assay and RRT (Relative Retention Time) of all

individual known impurities were evaluated. From the above study the proposed method was found to be

robust.

9.156 Impurity - A

195.9

254.8270.2296.3 348.8 389.4

AU

0.000

0.002

0.004

0.006

36.851 Maraviroc

198.2

257.2

AU

0.00

1.00

44.246 Impurity - B

195.9

257.2 292.8305.9322.5359.1

AU

0.000

0.005

0.010

nm

200.00 250.00 300.00 350.00 400.00

Fig.-3: (HPLC PDA Spectrums of Maraviroc Impurity A, Maraviroc and Maraviroc Impurity B)



Fig.-4: HPLC Chromatogram of Maraviroc Standard

Fig.-5: HPLC Chromatogram of Maraviroc Impurity A

Fig.-6: HPLC Chromatogram of Maraviroc Impurity B



Fig.-7: HPLC Chromatogram of Maraviroc Blank

Fig.-8: HPLC Chromatogram of Maraviroc placebo

Fig.-9: HPLC sample Chromatogram of Maraviroc spiked sample



Fig.-10: HPLC sample Chromatogram of Maraviroc Unspiked sample

Fig.-11: HPLC Chromatogram of Maraviroc and its degradation impurites at 5N HCl

Fig.-12: HPLC Chromatogram of Maraviroc and its degradation impurites at 2N NaOH.



Fig.-13: HPLC Chromatogram of Maraviroc and its degradation impurites at 30%H2O2

Fig.-14: HPLC Chromatogram of Maraviroc and its degradation impurites from Thermal degradation

Fig.-15: HPLC Chromatogram of Maraviroc and its degradation impurites from UV degradation



Fig.-16: HPLC Chromatogram of Maraviroc and its degradation impurites from Humidity degradation

Fig.-17: HPLC Chromatogram of Maraviroc and its degradation impurites from water degradation

Fig.-18: Linearity of detector response graph of Maraviroc.



Fig. -19: Linearity of detector response graph of Maraviroc Impurity A.

Fig.-20: Linearity of detector response graph of Maraviroc Impurity B.

Table-1: Gradient Programme

Time(Minutes) Flow(mL/min) Mobile phase-A Mobile phase-B

0 0.8 100 0

3 0.8 100 0

50 0.8 10 90

59 0.8 10 90

60 0.8 100 0

70 0.8 100 0

Table-2:Gradient Programme

Time(Minutes)

Flow(mL/min) Mobile phase-A Mobile phase-B

0 1.5 90 10

5 1.5 90 10

15 1.5 50 50

20 1.5 40 60

30 1.5 30 70

40 1.5 30 70

42 1.5 90 10

50 1.5 90 10



Table-3: Gradient Programme

Time(Minutes) Flow(mL/min) Mobile phase-A Mobile phase-B

0 0.8 100 0

3 0.8 100 0

50 0.8 10 90

59 0.8 10 90

60 0.8 100 0

70 0.8 100 0

Table-4: System Suitability Report For Related Substances

Compound Retention

Time(minutes)*

Maraviroc

area/response*

USP Tailing* USP Plate

count*

%RSD*

Maraviroc 37.7 67731 0.9 374340 0.63

*Number of standard injections analysed are six.

Table-5: Relative Response Factors and Relative Retention Time

Component Name Relative Retention Time(RRT) Relative Response Factor(RRF)

Maraviroc 1.00 1.00

Impurity-A About 0.25 0.25

Impurity-B About 1.20 1.41

Table-6: Table Results for Specificity (Interference From Degradation Products)

Table-7: Table results for LOD and LOQ of Marviroc and its related impurities

Limit of

Detection Limit of Quantification

Component Name µg/mL µg/mL %RSD % Recovery

Maraviroc 0.0430 0.0989 3.2 99.3

Impurity-A 0.1521 0.3972 3.6 98.5

Impurity-B 0.0241 0.0485 3.0 99.1

Stress condition % Degradation Purity Angle Purity Threshold Peak purity

Pass/fail

Acid Stress(5N Hcl) 3.654 0.163 0.347 pass

Base Stress(2N NAOH) 0.184 0.166 0.338 pass

Oxidation Stress 21.796 0.152 0.348 pass

Photolytic Stress 0.167

0.189 0.355 pass

Thermal Stress 0.147

11 0.172 0.350 pass

Water Stress 0.201

0.202 0.356 pass

Humidity Stress 0.140

0.195 0.356 pass



Table-8: Linearity Report of Maraviroc

S.No.

Concentration

(mcg/mL) Area y-Best fit (Difference)2 Correlation Coefficient (R)= 0.9999

LOQ 0.0989 3406 2881 275966 Regression Coefficient (R2)= 0.9999

25% 0.4945 17030 16722 94583 y-Intercept= -579.77

50% 0.9890 33668 34025 127224 Slope of Regression line= 34989

75% 1.4835 51149 51327 31652 Residual Sum of squares= 1857813

100% 1.9781 67607 68633 1051931 Minimum Con in mcg/mL = 0.0989

150% 2.9671 103678 103237 194401 Maximum Con in mcg/mL = 3.9561

200% 3.9561 138128 137842 82057 y-Intercept at 100 % level = -0.858

Table-9: Linearity Report of Maraviroc Impurity A

S.No.

Concentration



25% 0.4965 3885 4001 13428 y-Intercept= -340.56

50% 0.9929 8245 8341 9303 Slope of Regression line= 8744.1




200% 3.9717 34326 34388 3890 y-Intercept at 100 % level = -2.034

Table-10: Linearity Report of Maraviroc Impurity B

S.No.

Concentration



25% 0.4874 25679 25471 43440 y-Intercept= 528.4

50% 0.9747 51136 50408 530518 Slope of Regression line= 51174




200% 3.8989 200525 200050 225201 y-Intercept at 100 % level = 0.537

Table-11: Results for precision of test method

%Impurity

S.No

Impurity -A Impurity -B

1 0.201 0.194

2 0.202 0.198

3 0.205 0.201

4 0.195 0.201

5 0.201 0.199



6 0.199 0.202

Mean 0.201 0.199

SD 0.0033 0.0029

%RSD 1.7 1.5

Table-12: Accuracy in the related substances determination of Maraviroc

(Impurity A)

Spike Level ‘µg/mL ’ added ‘µg/mL ’ found Mean %

recovery

50% 1.0031

000 0.9967 99.4

100% 2.0021 1.9877 99.3

150%. 3.0101 2.9620 98.4

200% 3.9561 3.9211 99.1

(Impurity B)

Spike Level ‘µg/mL ’ added ‘µg/mL ’ found Mean %

recovery

50% 0.9966

0.9811 98.4

100% 1.9819 1.9750 99.4

150%. 2.9879 2.9975 100.3

200% 3.9662 3.9910 100.6

Table-13: Bench top Stability of Maraviroc Test preparation and Standard Preparation

% Assay of test

preparation

Difference Time % Assay of

Standard

preparation

Difference

Impurity A Impurity B Impurity A Impurity B

Initial 99.5® NA* 0.205 0.203 NA* NA*

After 24 hours 99.1 0.4 0.200 0.196 0.005 0.007

After 48 hours

98.5 1.0 0.198 0.190 0.007 0.013

NA*----Not Applicable, ®--------Potency of Maraviroc on as is basis

Table-14: Refrigerator Stability of Maraviroc Test preparation and Standard Preparation

% Assay of test

preparation

Difference Time % Assay of

Standard

preparation

Difference

Impurity A Impurity B Impurity A Impurity B

Initial 99.5® NA* 0.205 0.203 NA* NA*

After 24 hours 99.2 0.3 0.201 0.198 0.004 0.005

After 48 hours

98.6

6

0.9 0.199 0.195 0.006 0.008

NA*----Not Applicable

®--------Potency of Maraviroc on as is basis.



CONCLUSION The proposed HPLC method is rapid, sensitive, precise and accurate for the determination of Maraviroc

and its related impurities and can be reliably adopted for routine quality control analysis of Maraviroc in

Bulk and its pharmaceutical formulations.

REFERENCES 1. www.drugbank.ca (Maraviroc)

2. www.rxlist.com (Maraviroc)

3. L. Satyanarayana, S.V. Naidu, M. Narasimha Rao, C. Ayyanna, and Alok Kumar; Research

Journal of Pharmaceutical Dosage Forms and Technology, 3(5), 230 (2011).

4. Masaaki Takahashi, Atsushi Hirano, Nami Okubo, Eri Kinoshita, Toshiharu Nomura and

Tsuguhiro Kaneda; The Journal of Medical Investigation, 57, 245 (2010).

5. Practical HPLC Method Development; Second Edition, Lloyd R. Snyder, Joseph J. Kirkland,

Joseph I. Glajch, (1997).

6. United States Pharmacopeia USP 34-NF 29, (2011).

7. ICH Guidelines on Validation of Analytical procedure: Text and Methodology Q 2 (R1), (2011).

[RJC-882/2012]

ijCEPr ISSN: 2229-3892(Print)

ISSN: 2229-5283(Online)

www.ijcepr.com

[April, August and December]

All articles will be peer-reviewed.

All submissions should be

addressed to the

Editor-in-Chief

by e-mail to:

[email protected]

International Journal of Chemical, Environmental and Pharmaceutical ResearchChemical, Environmental and Pharmaceutical ResearchChemical, Environmental and Pharmaceutical ResearchChemical, Environmental and Pharmaceutical Research

www.ijcepr.com [Abstracted in : Chemical Abstracts Service , American Chemical Society, USA and

CAB(I) , UK]

IJCEPR (the Journal) publishes original research papers in the advance and

dissemination of research findings in all related areas such as chemistry, environmental

engineering, environmental chemistry and pharmaceutics.

Scope and Coverage: The subject coverage by the Journal may be summarized as follows:

Chemistry section: Organic, Inorganic, Physical, Analytical, Biological, Industrial,

Agricultural & Soil, Petroleum, Polymers, Nanotechnology, Green Chemistry, Forensic,

Phytochemistry, Computational, as well as Chemical Physics and Chemical Engineering.

Environmental section: Environmental chemistry, wastewater treatment and

engineering, biosorption, chemisorption, heavy metal remediation, phytoremediation,

novel treatment processes for wastewaters, land reclamation methods, solid waste

treatment, anaerobic digestion, gasification, landfill issues, leachate treatment and

gasification.

Pharmaceutical section: drug discovery, over drug delivery to drug development,

medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics

and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery

including gene delivery, drug targeting, pharmaceutical technology, pharmaceutical

biotechnology and clinical drug evaluation

The Journal may also publish selected papers from conferences, book reviews and

reviews. Review articles would be generally solicited by the Editors from the experts.

STABILITY INDICATING HPLC METHOD FOR DETERMINATION OF...

Documents

Transcript of STABILITY INDICATING HPLC METHOD FOR DETERMINATION OF...