Utilization of Oxidation and Chelation reactions for Spectrophotometric Determination of Meropenem in Pharmaceutical Formulations

 

Srinivasa Rao Narala1*, K. Saraswathi2

1Department of Chemistry, R.V.R. and J.C. College of Engineering, Guntur, A.P., India.

2Department of Chemistry, S.V. University, Tirupathi, A.P., India.

*Corresponding Author E-mail: srinunarala@gmail.com

 

ABSTRACT:

Two new visible spectrophotometric methods (A and B) for the determination of Meropenem have been proposed. These methods are based on the oxidation of the drug with Fe (III) and the estimation of Fe (II) produced after chelation with either 1,10- Phenanthroline or Potassium Ferricyanide in acidic medium at 508nm (for method A) and at 780nm (for method B). The Beer’s law was obeyed in the concentration range of 1.0-4.0 µg/ml (for method A) and 2.0-10µg/ml (for method B). Thus results of the proposed methods were validated statistically and applied successfully for the determination of Meropenem in bulk and its dosage forms.

 

KEYWORDS: Meropenem, Spectrophotometry, Oxidation, Recovery experiments.

 

 


INTRODUCTION: 

Meropenem is chemically (4R, 5S, 6s) – 3- [ (2S, 5S)5- (Di methyl carbamoyl) pyrrolidin-2-yl] sulfanyl – 6 – (1- hydroxy ethyl) – 4 – methyl – 7 –oxo – 1- aza bicyclo [3.2.0] hept -2 ene-2-carboxylic acid. It is a broad–spectrum carbapenem antibiotic and is active against Gram-positive and Gram – negative bacteria, exerts its action by penetrating bacterial cells readily and interfering with the synthesis of vital cell wall components, which leads to cell death. A very few physico-chemical methods1-30 appeared in the literature for the determination of Meropenem in serum and in pharmaceutical formulations, which include spectrophotometric, HPLC, liquid chromatographic and electrophoresis techniques. The analytically important functional groups of Meropenem are not fully exploited for designing suitable spectrophotometric methods for its determination.

 

Hence the author made an attempt and succeeded in developing certain sensitive, precise and accurate spectrophotometric methods.

 

MATERIALS AND METHODS:

Apparatus:

All spectral and absorbance measurements were made on a Techcomp UV–2301 UV-Visible spectrophotometer with 1cm matched quartz cells.

 

Chemicals and reagents:

All chemicals used were of analytical grade. Meropenem (pharmaceutical grade) was obtained from local pharmaceutical laboratory and commercial formulations were procured from the market. Aqueous solutions of 1, 10- Phenanthroline (0.01M), Ferric chloride (0.003M) and Ortho phosphoric acid (0.2M) were prepared for method A. Aqueous solutions of Ferric chloride (0.5% w/v), Potassium ferricyanide (0.2% w/v) and 1N HCl were prepared for method B.

 

Preparation of standard solution:

About 100mg of Meropenem was accurately weighed and transferred into a 100ml volumetric flask and diluted to volume with methanol to get the stock solution (1mg/ml). From this, suitable dilutions were made to obtain a final working concentration of 50 µg/ml (for method A) and 100µg/ml (for method B).

 

 

Preparation of sample solution:

Accurately weighed formulation powder equivalent to 100mg of Meropenem was transferred to a 100ml volumetric flask. About 20ml of methanol was added and sonicated for 10min. finally made up the volume with methanol and mixed thoroughly. The resulting solution was filtered through a Whatman filter paper. From this, suitable dilutions were made to obtain the concentration of 50µg/ml (for method A) and 100µg/ml (for method B).

 

Procedure for Calibration Curve:

In method A, different aliquots of working standard solution of Meropenem (50µg/ml) ranging from 0.5 – 5 ml were added to a series of heating tubes. To each tube 1ml of ferric chloride and 1ml of 1,10-Phenanthroline were added and heated for 15min. at 100°C on a water bath and then cooled to room temperature and 2ml of ortho phosphoric acid was added. The contents of the tubes were transferred to a series of 25ml standard flasks, then diluted to the mark with distilled water. The absorbance of each solution was measured at 508nm against the reagent blank. The calibration graph was constructed by plotting the absorbance versus concentration of the drug. The concentration of unknown was read from the calibration graph (Fig. 1).

 

 

 

In method B, different aliquots of working standard solution of Meropenem (100µg/ml) ranging from 0.5 – 5ml were transferred to a series of 25ml standard flasks. To each flask 1 ml of ferric chloride and 2ml of Potassium ferri cyanide were added and kept for 10min. To this 1ml of 1 N HCl is added and the volume is made up to the mark with distilled water. The absorbance of each solution was measured at 780nm against the reagent blank and the calibration graph was constructed.

 

The concentration of unknown was read from the calibration graph (Fig. 2).

 

 

RESULTS AND DISCUSSION:

The proposed methods are based on the oxidation of Meropenem by ferric salt and the reduced state of iron was utilized for the formation of colored complex on treatment with 1,10 -Phenanthroline or Potassium ferri cyanide in acidic medium. Optical characteristics such as molar absorptivity, sandell’s sensitivity, precision and accuracy are summarized in Table-1. The relative standard deviation and confidence limits were considered satisfactorily for all these methods. The average drug content found by proposed methods is given in Table- 2.

 

Table 1: Optical characteristics of the proposed methods for Meropenem

S. No.

Parameter

Method A

Method B

1

λ max, nm

508

780

2

Beer’s law limits (µg/ml)

1.0 – 4.0

2.0 – 10.0

3

Molar absorptivity

(l mol-1 cm-1)

0.6695×104

2.0032×103

4

Sandell’s sensitivity

(µg cm-2)

0.0573

0.1914

6

Regression equation

(Y= mX+b)

 

 

Slope (m)

0.4149

0.1304

Intercept (b)

0.0370

-0.1053

7

Correlation coefficient (r)

0.9995

0.9808

8

Relative Standard Deviation (%)*

0.8158

0.4356

9

% Range of error (Confidence limits)

 

 

0.05 level

± 1.0128

± 0.5419

0.01 level

± 1.6797

± 0.8988

* Mean of five determinations


 

Table 2: Assay of Meropenem in commercial formulations by proposed methods

Formu

Lation

Labeled Amount mg/vial

Method A

Method B

Amount found*

% Recovery**

Amount found*

% Recovery**

A

500

499.90 ± 0.058

99.75 ± 0.238

499.81 ± 0.095

99.95 ± 0.021

B

500

499.92 ± 0.035

99.59 ± 0.410

499.90 ± 0.027

99.40 ± 0.414

C

500

499.97 ± 0.052

99.76 ± 0.252

499.89 ± 0.061

99.89 ± 0.036

 

* Mean±standard deviation of five determinations.

**Mean±standard deviation of three determinations.


The characteristics of the proposed methods summarized in table -1 clearly indicate that the reagents 1,10-Phenanthroline and Potassium ferricyanide in acidic medium can be successfully employed for the determination of Meropenem. The low standard deviation and high percent recovery values shows that precision and accuracy of the methods are satisfactory. The results obtained in the determination of Meropenem in commercial formulations listed in table-2 are very close to that of manufacturers specifications.

 

CONCLUSION:

The proposed methods are simple, accurate, sensitive and are suitable for the determination of Meropenem in pharmaceutical formulations without interference from the excipients and also for quality control in the pharmaceutical laboratories.

 

ACKNOWLEDGEMENTS:

I would like to acknowledge the contribution of my research supervisor Prof. K. Saraswathi with whose help I was able to incorporate this work in my thesis. I tender grateful thanks to the Management and Principal, R.V.R. and J.C. College of Engineering, Guntur for their encouragement to me for doing this work.

 

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Received on 17.08.2024      Revised on 10.12.2024

Accepted on 27.03.2025      Published on 01.12.2025

Available online from December 06, 2025

Research J. Pharmacy and Technology. 2025;18(12):5861-5863.

DOI: 10.52711/0974-360X.2025.00846

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