A Validated Stability-Indicating UHPLC Method for Determination of Naproxen and Its Related Compounds in Bulk Drug Samples

K. Tirumala Rao, L. Vaikunta Rao

Analytical Research, Product and Technology Development, Ecologic Technologies Limited, Hyderabad, India.
Department of Chemistry, Gitam Institute of Science, GITAM University, Visakhapatnam, India.

DOI: 10.4236/ajac.2013.46036                

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.

Keywords

Naproxen; Stability-Indicating; Related Substances; Assay; Validation; UHPLC

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	USP, “Monograph of Naproxen Sodium,” 34th Edition, United States Pharmacopoeial Convention, Rockville, 2011.
[2]	ICH, “Stability Testing of New Drug Substances and Products,” International Conference on Harmonization Guidance Documents, Q1A (R2), 2005.
[3]	ICH, “Impurities in New Drug Substances,” International Conference on Harmonization Guidance Documents, Q3A (R1), 2006.
[4]	ICH, “Impurities in New Drug Products,” International Conference on Harmonization Guidance Documents, Q3B (R1), 2006.
[5]	EP, “Monograph of Naproxen Sodium,” 7th Edition, European Pharmacopeia Guideline Document, 2011.
[6]	J. Peter, Harrington and E. Lodewijk, “Twenty Years of Naproxen Technology,” Organic Process Research and Development, Vol. 1, No. 1, 1997, pp. 72-76. doi:10.1021/op960009e
[7]	H. Zhu and M. A. Bo, “Asymmetric Hydrogenation Synthesis of –(S)-(+)-2-(6’-Methoxyl-2-naphthyl) Propionic Acid by Cinchona Modified Pd (0)-α-FeOOH Catalyst,” Chinese Chemical Letters, Vol. 14, 2003, pp. 1101-1104.
[8]	A. Ekpe, J. H. Tong and L. Rodriguez, “High-Performance Liquid Chromatographic Method Development and Validation for the Simultaneous Quantitation of Naproxen Sodium and Pseudoephedrine Hydrochloride Impurities,” Journal of Chromatographic Science, Vol. 39, 2001, p. 81. doi:10.1093/chromsci/39.3.81
[9]	E. Dinc, A. Ozdemir, H. Aksoy, O. Ustundag and D. Baleanu, “Chemometric Determination of Naproxen Sodium and Pseudoephedrine Hydro Chloride in Tablets by HPLC,” Chemical and Pharmaceutical Bulletin, Vol. 54, 2006, p. 415. doi:10.1248/cpb.54.415
[10]	L. Monser and F. Darghouth, “Simultaneous Determination of Naproxen and Related Compounds by HPLC Using Porus Graphitic Carbon Column,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 32, 2003, p. 1087. doi:10.1016/S0731-7085(03)00213-9
[11]	B. M. Tashtoush and B. M. Al-Taani, “HPLC Determination of Naproxen in Plasma,” Die Pharmazie, Vol. 58, 2003, p. 614.
[12]	F. Nielsen-Kudsk, “HPLC Determination of Some Anti- Inflammatory, Weak Analgesic and Uricosuric Drugs in Human Blood Plasma and Its Application to Pharmacokinetics,” Acta Pharmacol Toxicol, Vol. 47, 1980, p. 267. doi:10.1111/j.1600-0773.1980.tb03653.x
[13]	T. M. Phillips and E. F. Wellner, “Measurement of Naproxen in Human Plasma by Chip-Based Immunoaffinity Capillary Electrophoresis,” Biomedical Chromatography, Vol. 20, 2006, p. 662. doi:10.1002/bmc.673
[14]	E. Mikami, T. Goto, T. Ohno, H. Matsumoto and M. Nishida, “Simultaneous Analysis of Naproxen, Nabumetone and Its Major Metabolite 6-Methoxy-n-Napthyl Acetic Acid in Pharmaceuticals and Human Urine by HPLC,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 23, 2000, p. 917. doi:10.1016/S0731-7085(00)00365-4
[15]	P. Zakeri_Milani, M. Barzegar-Jalali, H. Tajerzadeh, Y. Azrmi and H. Valizadesh, “Simultaneous Determination of Naproxen, Ketoprofen and Phenol Red in Samples from Rat Intestinal Permeability Studies HPLC Method Development and Validation,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 39, 2005, p. 624. doi:10.1016/j.jpba.2005.04.008
[16]	Y. Hsu, Y. Liou, J. Lee, C. Chen and A. Wu, “Assay of Naproxen by High-Performance Liquid Chromatography and Identification of Its Photo Products by LC-ESI/MS,” Biomedical Chromatography, Vol. 20, 2006, p. 787. doi:10.1002/bmc.598
[17]	ICH, “Validation of Analytical Procedures: Text and Methodology,” International Conference on Harmonization Guidance Documents, Q2 (R1), 2005.