STABILITY-INDICATING HPLC METHOD WITH FLUORESCENCE DETECTION FOR DETERMINATION OF METHOCARBAMOL IN TABLETS. APPLICATION TO THERAPEUTIC DRUG MONITORING

Abstract

A simple and highly sensitive stability-indicating HPLC method was developed and validated for the determination of the muscle relaxant, methocarbamol (MTC), in presence of its degradation product, guaifenesin (GFS). The analyses were carried out on a Nucleosil 100-5 phenyl column (4.6 × 250 mm, 5 µm particle size), using a mobile phase consisting of 0.02 M orthophosphoric acid/ acetonitrile mixture (80:20, v/v) of pH 5.0 at a flow rate of 1 mL/min with fluorescence detection at 277/313 nm. The method showed good linearity for MTC over the concentration range of 0.02–0.50 µg/mL with lower detection limit of 4.5 ng/mL and lower quantification limit of 14.0 ng/mL. The proposed method allowed the detection of GFS in MTC drug substance, as a potential impurity and degradation product, within the pharmacopeial limit specified by the USP. The proposed method was successfully applied for the determination of MTC in different pharmaceutical formulations without interference from coformulated drugs. Statistical comparison of the results obtained with those of the official method revealed no significance differences in the performance of the two methods regarding accuracy and precision. Moreover, the proposed method was applied for the therapeutic drug monitoring of MTC in human plasma.

Keywords:

• guaifenesin
• HPLC/fluorescence detection
• methocarbamol
• stability-indicating assay
• tablets
• therapeutic drug monitoring

Notes

*A = 0.02 M H₃PO₄; B = acetonitrile.

*Values between parentheses are the tabulated t and F values at P = 0.05, respectively.^{[ 22 ]}

^a Each result is the average of three separate determinations.

^a Each result is the average of three separate determinations.

*Values between parentheses are the tabulated t and F values at P = 0.05, respectively.^{[ 23 ]}