TITLE:
A Validated Stability-Indicating UHPLC Method for Determination of Naproxen and Its Related Compounds in Bulk Drug Samples
AUTHORS:
K. Tirumala Rao, L. Vaikunta Rao
KEYWORDS:
Naproxen; Stability-Indicating; Related Substances; Assay; Validation; UHPLC
JOURNAL NAME:
American Journal of Analytical Chemistry,
Vol.4 No.6,
June
20,
2013
ABSTRACT:
A simple, rapid, precise, accurate, rugged and robust
stability-indicating ultra-fast high performance liquid chromatographic
(UHPLC) method has been developed for the estimation of related compounds (imp-A,
imp-B, imp-C, imp-D and imp-E) in Naproxen and also the assay of Naproxen from
bulk drug samples. The stability indicating capability of the method was proven
by subjecting the samples to stress conditions such as acid, base, oxidation,
photolysis and thermal degradation. The efficient chromatographic separation
was achieved using mobile phase solution A prepared as buffer solution 10 mM monobasic potassium phosphate pH 4.0 ± 0.05 adjusted with diluted ortho
phosphoric acid solution and solution
B acetonitrile with linear gradient elution on poroshell 120 EC-C18 shot column (50 mm × 4.6
mm, 2.7 μm) and UV detection at 235 nm at a flow rate 1.0 mL/min, column oven
temperature was set to 25?C. The above are all known impurities and
degradation impurities are well resolved with Naproxen peak and these are
eluted within a 10 min runtime of HPLC. The photo diode array detector was used
for peak homogeneity testing during stress study experiments and the overall
mass balance was found to be 99.2% to 100.2% in all stress conditions. The
linear calibration range was
found to be 0.05 μg/mL to 0.75 μg/mL for related compounds and 50 μg/mL to 150
μg/mL for Naproxen and the
accuracy of the method was found to be 91.5% to 98.5% recovery for the related
substance method and 95.4% to 97.4% recovery for the assay method. The Naproxen
and related compounds were found to be stable up to 48 hours and the method
validation data show excellent results for precision, linearity, specificity,
limit of detection, limit of quantitation and robustness. The present method
can be successfully used for routine QC and stability studies and it will help
to reduce the analysis cost, time and effluent load compared to conventional
HPLC methods.