Novel validated stability-indicating UPLC method for the determination of Metoclopramide and its degradation impurities in API and pharmaceutical dosage form

Abstract

Aim

To develop a stability-indicating reversed phase ultra performance liquid chromatographic (RP-UPLC) method for the determination of related substances in Metoclopramide bulk drugs and pharmaceutical dosage form.

Method

The chromatographic separation was achieved using a Waters X-terra RP18 (150 × 4.6 mm), 3.5 μm particle size column using the gradient program with mobile phase consisting of solvent A: 30 mM monobasic sodium phosphate and 2.3 mM of pentane-1-sulphonic acid sodium salt (pH 3.0 buffer) and solvent-B (Acetonitrile). A flow rate of 1.2 mL/min and UV detector at 273 nm was used. The runtime was 18 min within which Metoclopramide and its four impurities, ACETYLMETO, ACMA, CLEE and ACME were well separated.

Results and discussion

The drug was subjected to stress conditions such as oxidative, acid & base hydrolysis, thermal and photolytic degradation. Metoclopramide was found to degrade significantly in photolytic, oxidative & thermal stress conditions and stable in acid, base, hydrolytic & humidity stress conditions. The major degradation impurities in oxidation and photolytic degradation were identified by LCMS. The degradation products were well resolved from the main peak and its impurities, thus proved the stability-indicating power of the method.

Conclusion

The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness. The calibration curves obtained for the four impurities were linear over the range 0.062–3.040 μg/mL.