Jeyashanthini Nalaiya, Sreenivasa Rao Sagineedu, Rajakumari Rajasingam, Zawahil Kassim, Mallikarjuna Rao Pichika


Objective: To develop a simple, selective and rapid stability-indicating reverse phase high performance liquid chromatography (RP-HPLC) method and validate as per ICH guidelines for simultaneous determination of simvastatin and niacin in a combined dosage form.

Methods: The chromatographic separation of the two cholesterol lowering drugs were achieved using Inertsil CN (5 µm, 250 mm x 4.6 mm i. d. column), maintained at 30 °C throughout the analysis. The drugs were separated in isocratic elution mode with a mobile phase of 0.1% acetic acid buffer-methanol (50:50, v/v) at a flow rate of 1.0 mL/min and a detection wavelength of 237 nm using a UV-PDA detector.

Results: The linearity and range for niacin and simvastatin were 0.05 to 0.150 mg/mL (R2> 0.9999) and 0.004 to 0.012 mg/mL (R2> 0.9992), respectively. Mean recoveries observed for niacin and simvastatin were 99.36% and 99.93%, respectively. The precision of the method obtained was 99.66% for niacin and 99.34% for simvastatin with a relative standard deviation less than 2%. The lower degree of % RSD that was obtained for intermediate precision has proved that the method is robust and rugged.

Conclusion: A simple and rapid stability-indicating RP-HPLC method was developed and validated for simultaneous determination of niacin and simvastatin in a combined dosage form and hence, it can be used in the quality control analysis of an active pharmaceutical ingredient and pharmaceutical dosage form.



Simvastatin, Niacin, RP-HPLC, Stability, Validation

| PDF | HTML |


Murtaza G. Solubility enhancement of simvastatin: a review. Acta Pol Pharm 2012;69:581-90.

Novakova L, Šatínský D, Solich P. HPLC methods for the determination of simvastatin and atorvastatin. TrAC Trend Anal Chem 2008;27(4):352-67.

Vosper H. Niacin: a re‐emerging pharmaceutical for the treatment of dyslipidaemia. Br J Pharmacol 2009;158(2):429-41.

The Unites States Pharmacopeia, 36th ed., The United States Pharmacopeial Convention: Rockville, MD; 2013. p. 1679-80.

Bays H. Safety of niacin and simvastatin combination therapy. Am J Cardiol 2008;101(8):S3-8.

Guyton JR, Bays HE. Safety considerations with niacin therapy. Am J Cardiol 2007;99(6):S22-31.

Guyton JR, Brown BG, Fazio S, Polis A, Tomassini JE, Tershakovec AM. Lipid-altering efficacy and safety of ezetimibe/simvastatin coadministered with extended-release niacin in patients with type IIa or type IIb hyperlipidemia. J Am Coll Cardiol 2008;51(16):1564-72.

Lyseng-Williamson KA. Niacin Extended Release (ER)/Simvastatin (Simcor®). Drugs RD 2010;10(4):253-60.

Ballantyne CM, Davidson MH, McKenney JM, Keller LH, Bajorunas DR, Karas RH. Comparison of the efficacy and safety of a combination tablet of niacin extended-release and simvastatin with simvastatin 80 mg monotherapy: the SEACOAST II (high-dose) study. J Clin Lipidol 2008;2(2):79-90.

Brown BG, Zhao X, Chait A, Fisher LD, Cheung MC, Morse JS, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345(22):1583-92.

Brown BG, Stukovsky KH, Zhao X. Simultaneous low-density lipoprotein-C lowering and high-density lipoprotein-C elevation for optimum cardiovascular disease prevention with various drug classes, and their combinations: a meta-analysis of 23 randomized lipid trials. Curr Opin Lipidol 2006;17(6):631-6.

Penn R, Williams III RX, Guha-Ray DK, Sawyers WG, Braun SL, Rains KT. An open-label, crossover study of the pharmacokinetics of Insoluble Drug Delivery®-Micro Particle fenofibrate in combination with atorvastatin, simvastatin, and extended-release niacin in healthy volunteers. Clin Ther 2006;28(1):45-54.

Insull Jr W, Basile JN, Vo AN, Jiang P, Thakkar R, Padley RJ. Efficacy and safety of combination therapy with niacin extended-release and simvastatin versus atorvastatin in patients with dyslipidemia: the supreme study. J Clin Lipidol 2009;3(2):109-18.

International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. Impurities in New Drug Substance ICH 3A; 2006.

Guzik L, Mrozik W, Kamysz W. Determination of simvastatin in pharmaceutical dosage forms by optimized and validated method using HPLC/UV. Croat Chem Acta 2010;83(4):371-7.

Seshukumar D, Abhishek G, Kona SS, Ravi SG, Vinod PS. Development and Validation of Stability indicating RP-UPLC method for simultaneous determination in fixed dose combination of ezetimibe and simvastatin. J Chromatogr Sep Tech 2012;3(3):1-7.

Drăghici I, Aramă C, Nedelcu A, Monciu C, Stănescu M, Tuchilă C. Development of a new LC method for the identification, separation and assay of simvastatin and its impurities. Farm 2013;61:229–39.

Liu M, Zhang D, Wang X, Zhang L, Han J, Yang M, et al. Simultaneous quantification of niacin and its three main metabolites in human plasma by LC–MS/MS. J Chromatogr B 2012;904:107-14.

Pfuhl P, Kärcher U, Häring N, Baumeister A, Tawab MA, Schubert-Zsilavecz M. Simultaneous determination of niacin, niacinamide and nicotinuric acid in human plasma. J Pharm Biomed Anal 2005;36(5):1045-52.

Thomas S, Bharti A, Tharpa K, Agarwal A. Quantification of potential impurities by a stability indicating UV-HPLC method in niacinamide active pharmaceutical ingredient. J Pharm Biomed Anal 2012;60:86-90.

British Pharmacopeia, Volume 3. Britain: Stationary Office; 2013.

European Pharmacopeia, 7thed Europe: Council of Europe; 2010.

International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human use. Validation of Analytical Procedures: Text Methodol ICH Q2 (R1); 2005.

Arayne MS, Sultana N, Hussain F, Ali SA. Validated spectrophotometric method for quantitative determination of simvastatin in pharmaceutical formulations and human serum. J Anal Chem 2007;62(6):536-41.

Lloyd RS, Joseph JK, Joseph LG. Practical HPLC Method development.2nd ed. USA: John Wiley & Sons Ltd; 1997.

Malenović A, Jančić-Stojanović B, Ivanović D, Medenica M. Forced degradation studies of simvastatin using microemulsion liquid chromatography. J Liq Chromatogr Rel Technol 2010;33(4):536-47.

Álvarez-Lueje A, Valenzuela C, Squella JA, Núñez-Vergara LJ. Stability study of simvastatin under hydrolytic conditions assessed by liquid chromatography. J AOAC Int 2005;88(6):1631-36.

Trone MD, McMicken NK, Thomas SM. Investigations into the HPLC retention behavior of simvastatin and structurally related compounds. J Liq Chromatogr Rel Technol 2005;28(17):2719-35.

About this article




Simvastatin, Niacin, RP-HPLC, Stability, Validation



Additional Links

Manuscript Submission


International Journal of Pharmacy and Pharmaceutical Sciences
Vol 7, Issue 2, 2015 Page: 262-268

Online ISSN


Authors & Affiliations

Jeyashanthini Nalaiya
International Medical University

Sreenivasa Rao Sagineedu
International Medical University

Rajakumari Rajasingam
International Medical University

Zawahil Kassim
Innovax Sdn.Bhd

Mallikarjuna Rao Pichika
International Medical University

Article Tools


  • There are currently no refbacks.