A Single Gradient Stability-Indicating Reversed-Phase LC Method for the Estimation of Impurities in Omeprazole and Domperidone Capsules

Abstract

A gradient reversed-phase liquid chromatographic (RP-LC) method was developed for the quantitative estimation of impurities in the pharmaceutical dosage form of Omeprazole and Domperidone capsules. The developed method is a stability-indicating test method for the estimation of impurities generated during the formulation and storage of Omeprazole and Domperidone capsules. The chromatographic separation was achieved on a column packed with octadecyl silane, having a column length of 250 mm and diameter of 4.6 mm with a particle size of 5 μm, and by following a gradient program using a combination of a monobasic potassium phosphate buffer (0.05M) and acetonitrile. Since the spectral properties were similar, both compounds' individual impurities were estimated at 285 nm. Forced degradation studies were performed on Omeprazole pellets (enteric coated) and Domperidone pellets (SR coated) encapsulated in size '1' hard gelatin capsules. Omeprazole and Domperidone were degraded using acid hydrolysis (0.1 N hydrochloric acid), base (0.1 N sodium hydroxide), oxidation (50% hydrogen peroxide), heat (105 °C), and UV light (254 nm). The established method was validated and found to be linear, accurate, precise, specific, robust, and rugged.

Keywords: Domperidone; Forced Degradation; Method validation; Omeprazole; RP-LC.

Fig. 1

Chemical structures of OM and DP

Fig. 2

Chemical structures of impurities

Fig. 2

Chemical structures of impurities

Fig. 3

The typical chromatogram of Diluent

Fig. 4

The typical chromatogram of Standard

Fig. 5

The typical chromatogram of Test preparation with spiked impurities

Fig. 6

The typical chromatogram of Placebo

Fig. 7

The typical Chromatogram of Sample in 1 M NaOH

Fig. 7a

Purity Plot of Omeprazole in 1M NaOH

Fig. 7b

Purity Plot of Domperidone in 1M NaOH

Fig. 8

The typical Chromatogram of Sample in 1 M HCl

Fig. 8a

Purity Plot of Omeprazole in 1M HCl

Fig. 8b

Purity Plot of Domperidone in 1M HCl

Fig. 9

The typical Chromatogram of Sample in 50% H₂O₂

Fig. 9a

Purity Plot of Omeprazole in 50% H2O2

Fig. 9b

Purity Plot of Domperidone in 50% H₂O₂

Fig. 10

The typical Chromatogram of Sample in Heat

Fig. 10a

Purity Plot of Omeprazole in Heat

Fig. 10b

Purity Plot of Domperidone in Heat

Fig. 11

The typical Chromatogram of Sample in UV

Fig. 11a

Purity Plot of Omeprazole in UV

Fig. 11b

Purity Plot of Domperidone in UV

Fig. 12

Linearity plot of Omeprazole C 789

Fig. 13

Linearity plot of Omeprazole N Oxide

Fig. 14

Linearity plot of Omeprazole Desmethoxy impurity

Fig. 15

Linearity plot of Omeprazole Sulphone

Fig. 16

Linearity plot of Omeprazole Sulphide

Fig. 17

Linearity plot of Domperidone Imp-A

Fig. 18

Linearity plot of Domperidone Imp-B

Fig. 19

Linearity plot of Domperidone Imp-C

Fig. 20

Linearity plot of Domperidone Imp-D

Fig. 21

Linearity plot of Domperidone Imp-F