Chemometrics-Assisted UV Spectrophotometric and RP-HPLC Methods for the Simultaneous Determination of Tolperisone Hydrochloride and Diclofenac Sodium in their Combined Pharmaceutical Formulation.

Nikunj Rameshbhai Gohel

doi:10.3797/scipharm.1306-01

Abstract

Chemometrics-assisted UV spectrophotometric and RP-HPLC methods are presented for the simultaneous determination of tolperisone hydrochloride (TOL) and diclofenac sodium (DIC) from their combined pharmaceutical dosage form. Chemometric methods are based on principal component regression and partial least-square regression models. Two sets of standard mixtures, calibration sets, and validation sets were prepared. Both models were optimized to quantify each drug in the mixture using the information included in the UV absorption spectra of the appropriate solution in the range 241–290 nm with the intervals λ = 1 nm at 50 wavelengths. The optimized models were successfully applied to the simultaneous determination of these drugs in synthetic mixture and pharmaceutical formulation. In addition, an HPLC method was developed using a reversed-phase C18 column at ambient temperature with a mobile phase consisting of methanol:acetonitrile:water (60:30:10 v/v/v), pH-adjusted to 3.0, with UV detection at 275 nm. The methods were validated in terms of linearity, accuracy, precision, sensitivity, specificity, and robustness in the range of 3–30 μg/mL for TOL and 1–10 μg/mL for DIC. The robustness of the HPLC method was tested using an experimental design approach. The developed HPLC method, and the PCR and PLS models were used to determine the amount of TOL and DIC in tablets. The data obtained from the PCR and PLS models were not significantly different from those obtained from the HPLC method at 95% confidence limit.

Highlights

Tolperisone hydrochloride (TOL), chemically 2-methyl-1-(4-methylphenyl)-3-(1-piperidin-1yl)propane-1-one, is a piperidine derivative and the structure is shown in Fig. 1 [1]
The linear range for each drug was determined by plotting the absorbance at its λmax (TOL, 256 nm and Diclofenac sodium (DIC), 282 nm) versus the sample concentration
Principal component regression (PCR) and partial least-square regression (PLS) models were successfully developed for the determination of TOL and DIC in a standard mixture set which did not contribute in the calibration set

Summary

Introduction

Tolperisone hydrochloride (TOL), chemically 2-methyl-1-(4-methylphenyl)-3-(1-piperidin-1yl)propane-1-one, is a piperidine derivative and the structure is shown in Fig. 1 [1]. Diclofenac sodium (DIC) is chemically the sodium salt of {2-[(2,6-dichlorophenyl)amino]phenyl}acetic acid and the structure is shown in Fig. 1 [1]. It is a non-steroidal antiinflammatory drug for the treatment of inflammatory conditions such as rheumatoid arthritis, osteoarthritis, and ankylosingspondilytis. The literature survey revealed that several analytical methods have been employed for the quantification of DIC, such as spectrophotometry [13], spectrofluorimetry [14], and chromatography [15]. The literature survey revealed that there are several analytical methods employed for the simultaneous quantification of TOL and DIC such as spectrophotometry [16] and HPTLC [17]

Objectives

Methods

Results

Conclusion