PPT ON RP-HPLC METHOD DEVELOPMENT FOR SIMULTANEOUS ESTIMATION OF ATORVASTATIN AND TELMISARTAN

BY M. VIJAYA KRANTHI

S. SUMAS. SAI SNEHAV. BHAVYA

S.SUNILK.DURGA RAJ

under the guidanceMISS. N. SWETHA

(PHARMACEUTICAL ANALYSIS AND QUALITY CONTROL)RGR SIDDHANTHI COLLEGE OF PHARMACY

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.

METHOD VALIDATION

• SPECIFICITY

• SELECTIVITY

• PRECISION

• REPEATABILITY

• INTERMEDIATE PRECISION

• REPRODUCIBILITY

• ACCURACY

• LINEARITY

• RANGE

• LIMIT OF DETECTION

• LIMIT OF QUANTIFICATION

• RUGGEDNESS

• ROBUSTNESS

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.

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 VALUES 0.55 ± 0.02 AND 0.41 ± 0.02𝑅 𝑓

• 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

• 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.

 

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.

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.

DRUG PROFILE

ATORVASTATIN

STRUCTURE:

MOLECULAR FORMULA :C33H55FN2O5SOLUBILITY: soluble in methanol, ethanolCATEGORY: HMGcoA reductase inhibitor

TELMISARTAN

• STRUCTURE

STRUCTURE:

MOLECULAR FORMULA: C33H30N4O2SOLUBILITY : freely solubke in methanol, ethanol and butanolCATEGORY: anti- hypertensiveCLASS : Angiotensin-II receptor type 1

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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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CHEMICALS AND SOLVENTS USED• ACETONITRILE : HPLC GRADE, QUALIGENS FINE

CHEMICALS, MUMBAI.• HPLC WATER : QUALIGENS FINE CHEMICALS, MUMBAI. •  • METHANOL : HPLC GRADE, QUALIGENS FINE • ORTHOPHOSPHORIC ACID : 88% GR, MERCK, MUMBAI. • TRIETHYLAMINE : S.D. FINE CHEMICALS LTD., MUMBAI.• PHOSPHATE BUFFER : S.D. FINE CHEMICALS LTD., MUMBAI.• METHANOL : LR GRADE S.D. FINE CHEMICALS LTD., MUMBAI.

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INSTRUMENTS• SCHIMADZU DIGITAL ELECTRONIC BALANCE- BL 220H.• LAB INDIA SAB 5000, PH METER.• VALUE VACCUM PUMP.• SCHIMADZU HPLC, PHENOMENEX COLUMN, UV DETECTOR.• ULTRASONIC CLEANER, LIFE CARE EQUIPMENTS PVT.LTD.

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

PEAKS

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

10mm phosphate buffer: acetonitrile ( 30: 70)

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.

RESULTS AND DISCUSSIONS

• 10MM PHOSPHATE BUFFER WAS FOUND TO BE IDEAL FOR THE WORK.• PHOSPHATE BUFER ADJUSTED TO PH-3 WITH ORTHOPHOSPHORIC ACID GAVE

GOOD PEAKS .• THE RETENTION OF ATORVASTAIN AND TELMISARTAN WAS FOUND TO BE 3.2

AND 4.6 MINUTES RESPECTIVELY.• THE LOD OF ATORVASTATIN AND TELMISARTAN WAS FOUND TO BE

0.20MICROGRAM PER ML AND 0.11MICROGRAM PER ML.• THE LOQ OF ATORVASTATIN AND TELMISARTAN WERE FOUND TO BE 0.32

MICRO GRAM PER ML AND 0.39 MICROGRAM PER ML RESPECTIVELY.• THE DEVELOPED METHOD WAS FOUND TO BE ROBUST.

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.

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.

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