DEVELOPMENT AND VALIDATION OF A STABILITY INDICATING RP-LC METHOD FOR THE ESTIMATION OF PROCESS RELATED IMPURITIES AND DEGRADATION PRODUCTS OF DULOXETINE HYDROCHLORIDE AND PHTHALIC ACID IN DULOXETINE HYDROCHLORIDE DELAYED RELEASE CAPSULES

Abstract

A stability-indicating gradient reverse phase liquid chromatographic method was developed for the quantitative determination of process related impurities and forced degradation products of duloxetine hydrochloride, duloxetine phthalamide impurity, and phthalic acid in duloxetine hydrochloride delayed release capsules. The method was developed by using Inertsil ODS-4 (150 mm × 4.6 mm) 3 µm column with mobile phase containing a gradient mixture of solvent A (0.02 M ammonium dihydrogen phosphate and 0.01 M 1-octane sulfonate sodium salt, pH adjusted to 2.5 with orthophosphoric acid) and B (750:300 mL mixture of acetonitrile and methanol). The flow rate of the mobile phase was 1.8 mL/min with column temperature of 50°C and detection wavelength at 230 nm. Duloxetine hydrochloride was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal, and photolytic degradation. Duloxetine hydrochloride was found to degrade significantly in acid, base and oxidative stress conditions. The degradation products were well resolved from phthalic acid, duloxetine and its impurities. The mass balance was found to be in the range of 95–105% in all the stressed conditions, thus proved the stability-indicating power of the method. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection and quantification, accuracy, precision and robustness.

Keywords:

• development
• duloxetine
• LC-MS
• phthalic acid
• stability-indicating
• validation

ACKNOWLEDGMENT

The authors are thankful to the management of Dr. Reddy's Laboratories Ltd., Hyderabad, India, for providing facilities to carry out this work.

Notes

^a Duloxetine; ^b Phthalic acid.

^a MUSI = Maximum un-specified impurity.

^b %Net degradation = % Degradation in stressed sample - % Degradation in unstressed sample.

ND = Not detected.

^a Amount of four impurities spiked with respect to 0.3% specification level and 1.5 mg/cap for PHA.

^b Mean ±RSD (%) for three determinations.

^a Peak-to-valley ratio between DLX and ADLX.