You are hereSPECTROPHOTOMETRIC METHOD FOR ESTIMATION OF MEROPENEM AND SULBACTAM SODIUM IN COMBINED DOSAGE FORM BY FIRST ORDER DERIVATIVE METHOD

SPECTROPHOTOMETRIC METHOD FOR ESTIMATION OF MEROPENEM AND SULBACTAM SODIUM IN COMBINED DOSAGE FORM BY FIRST ORDER DERIVATIVE METHOD


ABOUT AUTHORS:
Patel Sannil R*, Patel Satish A
Department of Quality Assurance,
Shree S. K. Patel College of Pharmaceutical Education & Research,
Ganpat University, Ganpat Vidyanagar – 384012, Mehsana, Gujarat, India.
*srpatel2200@gmail.com

ABSTRACT
The present manuscript describes simple, sensitive, rapid, accurate, precise and economical First order derivative spectrophotometry method for the simultaneous determination of Meropenem and Sulbactam Sodium in bulk and combined dosage form. The absorbance values at 333nm and 252 nm of first derivative spectrum was used for the estimation of Meropenem and Sulbactam Sodium, respectively without mutual interference. This method obeyed beer’s law in the concentration range of 5-70 μg/ml for Meropenem and 2-21 μg/ml for Meropenem. The method was successfully applied to pharmaceutical combined dosage form because no interference from the excipients was found. The suitability of this method for the quantitative determination of Meropenem and Sulbactam Sodiumwas proved by validation. The proposed method was found to be simple and sensitive for the routine quality control analysis of Meropenem and Sulbactam Sodium in bulk and combined dosage form. The results of analysis have been validated statistically and by recovery studies.


REFERENCE ID: PHARMATUTOR-ART-1781

INTRODUCTION
Meropenem, chemically 3-[5-(dimethylcarbamoyl) pyrrolidin-2-yl] sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo [3.2.0] hept-2-ene-2-carboxylic acid, is an anti-bacterial agent for systemic use1. The bactericidal activity of Meropenem results from the inhibition of cell wall synthesis. Meropenem readily penetrates the cell wall of most gram-positive and gram-negative bacteria to reach penicillin-binding- protein (PBP) targets. It is official in Indian Pharmacopoeia (IP)2. Literature survey reveals UV and HPLC methods for the estimation of Meropenem in pharmaceutical formulations5-8. Sulbactam is (R)-3, 3-dimethyl-7-oxo-4-thia-1-azabicyclo [3.2.0] heptane-2-carboxylic acid 4, 4-dioxide is a beta-lactamase inhibitor. Sulbactam is an irreversible inhibitor of beta-lactamase; it binds the enzyme and does not allow it to interact with the antibiotic. It is official in United States Pharmacopoeia (USP)3. Literature survey reveals UV and HPLC methods for the estimation of Sulbactam with other drugs in pharmaceutical formulations9-18. Literature survey also reveals spectrophotometric method based simultaneous equations for simultaneous estimation of Meropenem and Sulbactam in mixture by using 0.1M NaOH as a solvent4. The present communication describes simple, sensitive, rapid, accurate, precise and cost effective spectrophotometric method based on First order derivative spectrophotometry method for simultaneous estimation of both drugs in their combined  dosage form by using 0.1M KOH as a solvent .

MATERIALS AND METHODS
Apparatus

A shimadzu model 1700 (Japan) double beam UV/Visible spectrophotometer with spectral width of 2 nm, wavelength accuracy of 0.5 nm and a pair of 10 mm matched quartz cell was used to measure absorbance of all the solutions. Spectra were automatically obtained by UV-Probe 2.0 system software. A Sartorius CP224S analytical balance (Gottingen, Germany), an ultrasonic bath (Frontline FS 4, Mumbai, India) was used in the study.


Reagents and Materials
Meropenem (MERO) and Sulbactam Sodium (SUL) were kindly supplied as a gift samples from Montage Laboratories, Himmatnagar, Gujarat, India. The pharmaceutical formulation containing 1000 mg MERO and 500 mg SUL was kindly purchased from local market.  Potassium Hydroxide (S.D. Fine Chem Ltd., Mumbai)  and Whatman filter paper no. 41 (Millipore, USA) were used in the study.

Preparation of 0.1M Potassium Hydroxide Solution
An accurately weighed 5.611 gm Potassium Hydroxide Pallets were dissolved in 1000 ml distilled water.

Preparation of standard stock solutions
An accurately weighed quantity of standard MERO (10 mg) and SUL (10 mg) powder were transferred to 100 ml separate volumetric flasks and dissolved in 0.1 M KOH. The flasks were sonicated for 5 minutes and volumes were made up to mark with 0.1 M KOH to give a solution containing 100 μg/ml each of MERO and SUL.

Methodology
This method is based on First order derivative spectroscopy to overcome spectral interference from other drug. Zero order spectrums of both the drugs were converted to First order derivative spectra with the help of spectra manager software.

It was observed that MERO showed dA/dλ at 333 nm in contrast to SUL that has considerable dA/dλ at this wavelength. Further, MERO has zero dA/dλ at 252 nm while at this wavelength SUL has significant dA/dλ. Therefore wavelengths 333 nm and 252 nm were employed for the determination of MERO and SUL respectively without interference of other drug. The calibration curves were plotted at these two wavelengths of concentrations against dA/dλ separately. Eight working standard solutions having concentration 5, 10, 20, 30, 40, 50, 60, 70 μg/ml for MERO and 2, 3, 6, 9, 12, 15, 18, 21 μg/ml for SUL were prepared in 0.1 M KOH from the mixture and the absorbances at 333 nm (zero crossing point for SUL) and 252 nm (zero crossing point for MERO) were measured and the calibration curves were plotted at these wavelengths.

Validation of the proposed method
The proposed method was validated according to the International Conference on Harmonization (ICH) guidelines19

Linearity (calibration curve)
The calibration curves were plotted over a concentration range of 5-70 µg/ml for MERO and    2-21 µg/ml for SUL. Accurately measured standard solutions of MERO (0.5, 1, 2, 3, 4, 5, 6, 7ml) and SUL (0.2, 0.3, 0.6, 0.9, 1.2, 1.5, 1.8, 2.1ml) were transferred to a series of 10 ml of volumetric flasks and diluted to the mark with 0.1 M KOH. The absorbances of the derivatised spectra were measured at 333 nm and 252 nm for MERO and SUL respectively against 0.1 M KOH as blank. Six replicate analysis were carried out. Absorbance Vs concentration were plotted to obtain the calibration graph. Both drugs obey the Beer‘s law with the above concentration range with R2 value of 0.9989 and 0.9983 for MERO and SUL, respectively.

Method precision (repeatability)
The precision of the instrument was checked by repeated scanning and measurement of absorbance of solutions (n = 6) for 20 µg/ml MERO and SUL 9 µg/mlwithout changing the parameter of the proposed spectrophotometry method.

Intermediate precision (reproducibility)
The intraday and interday precision of the proposed method was determined by analyzing the corresponding responses 3 times on the same day and on 3 different days over a period of 1 week for 3 different concentrations of standard solutions of MERO and SUL(20, 30, 40 µg/ml for MEROand 9, 12, 15 µg/ml for SUL). The result was reported in terms of relative standard deviation (% RSD).

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