method validation,drug profile,materials and method process,instruments,method development,analysis,results.

1. SIMULTANEOUS
ESTIMATION
M. VIJAYA KRANTHI
S. SUMA
S. SAI SNEHA
V. BHAVYA
S.SUNIL
K.DURGA RAJ
. N. SWETHA
(PHARMACEUTICAL ANALYSIS AND QUALITY CONTROL)
RGR SIDDHANTHI COLLEGE OF PHARMACY

2. INTRODUCTION
HPLC
HIGH PERFORMANCE LIQUID CHROMATOGRAPHY IS A VERY SENSITIVE ANALYTICAL TECHNIQUE
MOST WIDELY USED FOR THE QUALITATIVE AND QUANTITATIVE ANALYSIS OF PHARMACEUTICALS.
RP-HPLC
• IT INVOLVES THE USAGE OF NON-POLAR STATIONARY PHASE SUCH AS HYDROCARBON AND
POLAR MOBILE PHASE SUCH AS WATER, METHANOL OR ACETONITRILE.
• IN REVERSE PHASE CHROMATOGRAPHY THE SOLUTES ARE ELUTED IN THE ORDER OF THEIR
DECREASING POLARITIES.
PRINCIPLE
IT IS BASED ON THE PRINCIPLE OF PARTITION COEFFICIENT.

3. METHOD VALIDATION
• SPECIFICITY
• SELECTIVITY
• PRECISION
• REPEATABILITY
• INTERMEDIATE PRECISION
• REPRODUCIBILITY
• ACCURACY
• LINEARITY
• RANGE
• LIMIT OF DETECTION
• LIMIT OF QUANTIFICATION
• RUGGEDNESS
• ROBUSTNESS

4. INTRODUCTION TO THE DRUGS TO BE ESTIMATED AND ITS METHOD
DEVELOPMENT
• ATORVASTATIN CALCIUM IS THE CALCIUM SALT, A HMGCOA REDUCTASE .
• TELMISARTAN IS A POTENT , LONG-LASTING NONPEPTIDE ANTAGONIST OF THE
ANGIOTENSIN II RECEPTOR THAT IS INDICATED FOR THE TREATMENT OF
ESSENTIAL HYPERTENSION.

5. LITERATURE REVIEW
• PRAJAKTA S. NAWALE, ATUL A. SHIRKHEDKAR, SANJAY J. SURANA, AND AMOD S. PATIL, REPORTED
SIMULTANEOUS ESTIMATION OF TELMISARTAN AND METOPROLOL SUCCINATE BY RP-HPTLC METHOD FROM
COMBINED TABLET DOSAGE FORM. THE MOBILE PHASE CONSISTS OF METHANOL: WATER: TRIETHYLAMINE (6:
4:0.5 V/V) AND THE PH WAS ADJUSTED TO 5.5 BY ADDING TRIETHYLAMINE. THE DETECTION WAVELENGTH WAS
242NM. TELMISARTAN AND METOPROLOL SHOWED 𝑅 𝑓 VALUES 0.55 ± 0.02 AND 0.41 ± 0.02
• KRISHNA R GUPTA, ET AL., REPORTED SIMULTANEOUS ESTIMATION OF ATORVASTATIN AND ATENOLOL IN
PHARMACEUTICAL DOSAGE BY REVERSE PHASE HPLC. THE MOBILE PHASE CONSISTS OF PHOSPHATE BUFFER AND
ACETONITRILE (28:72%V/V) WITH PH ADJUSTED TO 4.58 WITH DILUTE ORTHOPHOSPHORIC ACID. FLOW RATE
WAS 1ML/MIN WITH DETECTION WAVELENGTH AT 238NM. THE RETENTION TIME OF ATORVASTATIN WAS
2.1MIN AND ATENOLOL WAS 3.7MIN.
• VIJAYKUMAR G, MURTHY TEGK, REPORTED SIMPLE HPLC METHOD FOR THE DETERMINATION OF
TELMISARTAN IN SERUM SAMPLES. THE MOBILE PHASE CONSISTS OF 0.01M POTASSIUM DIHYDROGEN
ORTHOPHOSPHATE AND ACETONITRILE(35:65,V/V). THE DETECTION WAVELENGTH WAS MONITORED AT 282NM
AND THE RETENTION

6. • SUBHAKAR, ET AL., REPORTED DEVELOPMENT AND VALIDATION OF RP-HPLC
METHOD FOR THE ANALYSIS OF TELMISARTAN USING C18 COLUMN. THE MOBILE
PHASE USED WAS POTASSIUM DI-HYDROGEN PHOSPHATE AND ACETONITRILE
(60:40% V/V). THE FLOW RATE WAS 1ML/MIN. THE DETECTION WAVELENGTH WAS
MONITORED AT 243NMAND THE RETENTION TIME WAS FOUND TO BE 3.4 MIN WITH
SYMMETRIC PEAKS.
• JAIN N, RAGHUWANSHI R, DEEPTHI JAIN, DEVELOPED A METHOD FOR
SIMULTANEOUS ESTIMATION OF ATORVASTATIN CALCIUM AND FENOFIBRATE BY
RP-HPLC METHOD IN TABLET DOSAGE FORM. THE MOBILE PHASE CONSISTS OF
METHANOL AND ACETATE BUFFER (82:18 V/V) AND THE PH WAS ADJUSTED TO 3.7.
FLOW RATE OF 1.5ML/MIN WAS MAINTAINED. THE DETECTION WAVELENGTH WAS
248NM. THE RETENTION TIME FOR ATORVASTATIN CALCIUM AND FENOFIBRATE
WAS FOUND TO BE 3.02 AND 9.05.

7. OBJECTIVE
• MULTICOMPONENT FORMULATIONS HAVE THE ADVANTAGE OF ALLOWING FEWER
DOSES TO BE TAKEN WITH POTENTIALLY ENHANCING COMPLIANCE.
• THE MAIN OBJECTIVE IS TO TO DEVELOP SIMPLE, ACCURATE, SENSITIVE, RAPID AND
ECONOMIC METHOD AND VALIDATE ALL THE METHODS TO ENSURE THEIR ACCURACY,
PRECISION, REPEATABILITY FOR SIMULTANEOUS ESTIMATION OF ATORVASTATIN AND
TELMISARTAN FROM COMBINED DOSAGE FORMS USING UV – VISIBLE
SPECTROSCOPY AND HIGH PERFORMANCE LIQUID CHROMATOGRAPHY.

8. AIM AND PLAN
AIM
PRESENT WORK AIMS AT DEVELOPING A SIMPLER, SENSITIVE, PRECISE, ECONOMIC
AND VALIDATED STABILITY INDICATING RP-HPLC METHOD FOR THE SIMULTANEOUS
ANALYSIS OF ATORVASTATIN AND TELMISARTAN IN TABLET DOSAGE FORM.
PLAN
DEVELOPMENT AND VALIDATION OF STABILITY INDICATING RP-HPLC METHOD FOR
THE SIMULTANEOUS ESTIMATION OF ATORVASTATIN AND TELMISARTAN IN BULK AND
PHARMACEUTICAL DOSAGE FORM.

9. DRUG PROFILE
ATORVASTATIN
STRUCTURE:
MOLECULAR FORMULA :C33H55FN2O5
SOLUBILITY: soluble in methanol, ethanol
CATEGORY: HMGcoA reductase inhibitor

10. TELMISARTAN
•
STRUCTURE:
MOLECULAR FORMULA: C33H30N4O2
SOLUBILITY : freely solubke in methanol, ethanol and butanol
CATEGORY: anti- hypertensive
CLASS : Angiotensin-II receptor type 1

11. MATERIALS AND METHODOLOGY
PURE DRUG SAMPLES
BOTH THE DRUG SAMPLES OF ATORVASTATIN AND TELMISARTAN WERE
PURCHASED FROM THE DRUG DEALERS IN HYDERABAD.
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13. INSTRUMENTS
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14. METHOD DEVELOPMENT
• WAVE LENGTH – 245NM
• MOBILE PHASE :10MM PHOSPHATE BUFFER GAVE SYMMETRICAL PEAKS WITH GOOD
RESOLUTION., RF OF ATORVASTATIN IS 3.2 MINUTES AND TELMISARTAN IS 4.6 MINUTES.
• OPTIMIZAION OF SEPARATION CONDITIONS IS BASED ON THE FOLLOWING FACTORS :
1. EFFECT OF STRENGTH OF PHOSPHATE BUFFER
2. EFFECT OF RATIO OF MOBILE PHASE
3. EFFECT OF PH

15. PEAKS
Water: Acetonitrile 30:70 20mm phosphate buffer :
acetonitrile(30:70)

16. 10mm phosphate buffer: acetonitrile ( 30: 70)

17. ANALYSIS OF FORMULATION
• PREPARATION OF STANDARD SOLUTION:
• ALIQUOTS OF STANDARD SOLUTION CONTAINS 5 TO 50MICROGRAM PER ML
OF ATORVASTATIN AND TELMISARTAN.
• PREPARATION OF SAMPLE SOLUTION:
• 10 MG OF ARBITEL-AV DISSOLVED IN MOBILE PHASE
• FINAL VOLUME WAS MADE UPTO GET A WORKING CONCENTRATION OF 20
MICROGRAM PER ML EACH OF ATORVASTATIN AND TELMISARTAN.

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19. CONCLUSION
A SIMPLE , SPECIFIC, LINEAR, PRECISE AND ACCURATE RP-HPLC METHOD HAS BEEN
DEVELOPED AND VALIDATED FOR QUANTITAVE DETERMINATION OF ATORVASTATIN
AND TELMISARTAN IN NEW TABLET FORMULATION.
THE METHOD IS VERY SIMPLE AND SPECIFIC AS BOTH PEAKS ARE WELL SEPARATED
FROM ITS EXCIPIENT PEAKS AND WITH TOTAL RUNTIME OF 5 MIN, MAKES THE
DEVELOPED METHOD ITS SUITABLE FOR ROUTINE QUALITY CONTROL ANALYSIS WORK.

20. REFERENCES
• SETHI, P.D., QUANTITATIVE ANALYSIS OF DRUGS IN PHARMACEUTICAL
FORMULATION, 3RDEDN. CBS PUBLISHERS AND DISTRIBUTORS. 1997. PP. 3.
• ARTHUR I. VOGEL., ELEMENTARY PRACTICAL ORGANIC CHEMISTRY PART 2:
QUALITATIVE ORGANIC ANALYSIS. 2NDEDN. PP. 241.
• DOUGLAS A., SKOOG., PRINCIPLES OF INSTRUMENTAL ANALYSIS. (399)
• BECKETT, A.H., STENLAKE, J.B., PRACTICAL PHARMACEUTICAL CHEMISTRY 2,
4THEDN., CBS PUBLISHERS AND DISTRIBUTORS. 1997. PP. 275, 281,307.
• WILLARD. DEAN., SETTLE., INSTRUMENTAL METHOD OF ANALYSIS, 6TH EDN.1988.
(77)
• SYNDER., JOSEPH, J., KIRKLAND., J. L., GLAJC., PRACTICAL HPLC METHOD
DEVELOPMENT. 2NDEDN., JOHN WILEY AND SONS, INC. 1997. (7)

21. • GURUDEEP R. CHATWAL., SHAM K. ANAND., INSTRUMENTAL METHODS OF
CHEMICAL ANALYSIS. 5THEDN., HIMALAYA PUBLISHING HOUSE. 2002. PP.2.624-
2.625.
• FOOD AND DRUG ADMINISTRATION. GUIDANCE FOR INDUSTRY: ANALYTICAL
PROCEDURES AND METHODS VALIDATION (DRAFT GUIDANCE). 2000. PP.501–504.
• ICH, Q2 (R1). VALIDATION OF ANALYTICAL PROCEDURES. TEXT AND
METHODOLOGY. 2005.

22. • GODSE VP, DEODHAR MN. DEVELOPED AND VALIDATED A SPECTROSCOPIC METHOD
• FOR SIMULTANEOUS ANALYSIS OF ATORVASTATIN AND EZETIMIBEIN A PHARMACEUTICAL
• DOSAGE FORM. ASIAN J. RESEACH CHEM. 2009: 2 (1).
• PRATAP Y. PAWAR, MANISH A. RASKAR. SPECTROPHOTOMETRIC METHOD FOR
• SIMULTANEOUS ESTIMATION OF TELMISARTAN AND AMLODIPINE BESYLATE IN BULK AND
• TABLET FORMULATION.SCHOLARS RESEARCH LIBRARY,DERPHARMACHEMICA, 2012