A new HPLC method for selexipag analysis in pharmaceutical formulation and bulk form

Abstract

Selexipag is a new non-prostanoid prostacyclin receptor agonist used to treat pulmonary arterial hypertension. Selexipag is a long-acting IP receptor agonist with a shorter half-life than all other licensed drugs targeting the prostacyclin pathway, mostly administered intravenously or by subcutaneous infusion or inhalation. In this study, a new high performance liquid chromatography (HPLC) method was developed to analyze Selexipag in bulk and pharmaceutical formulations. The method used a column with Supelco Ascentis® Express (Sigma Aldrich, USA) model phenyl hexyl functional group (100×4.6 mm, ID, 2.7µm). Chromatographic separation was in isocratic elution mode, and the mobile phase mixture was acetonitrile containing 0.1% formic acid: water containing 0.1% formic acid (60:40, v/v) ratio. The method was linear in the concentration range of 15.7-117.6 µg/mL, and the LOD and LOQ were obtained as 2.4 and 3.1 µg/mL, respectively. Various method parameters have been tested according to the ICH Q2(R1) manual, and it is a method with high accuracy and precision. Therefore, the developed method is suitable for selexipag’s bulk and pharmaceutical formulation analysis.

Keywords

• Bulk
• HPLC
• Pharmaceutical formulation
• Selexipag

References

1. Scott LJJD. Selexipag: first global approval. Drugs. 2016;76:413-8. https://doi.org/10.1007/s40265-016-0549-4
2. Richter MJ, Gall H, Grimminger J, Grimminger F, Ghofrani H-A. Selexipag for the treatment of pulmonary arterial hypertension. Expert Opin Pharmacother. 2016;17(13):1825-34. https://doi.org/10.1080/14656566.2016.1215429
3. Xie S, Shi L, Chen J, Xu R-a, Ye X, Analysis B. Simultaneous quantification and pharmacokinetic investigation of selexipag and its main metabolite ACT-333679 in rat plasma by UPLC-MS/MS method. J Pharm Biomed Anal. 2020;190:113496. https://doi.org/10.1016/j.jpba.2020.113496
4. Gumustas M, Kurbanoglu S, Uslu B, Ozkan SA. UPLC versus HPLC on drug analysis: advantageous, applications and their validation parameters. J Chromatographia. 2013;76:1365-427. https://doi.org/10.1007/s10337-013-2477-8
5. Damireddy S, Pravalika K, Praveen M, Sathish G, Anusha M. Method development and validation of selexipag in its bulk and dosage form by rp-HPLC. J Int J Pharm Biol Sci. 2017;7:84. ISSN: 2230-7605
6. Youssef YM, Mahrouse MA, Mostafa E. Assessment of environmental impact of a novel stability-indicating RP-HPLC method and reported methods for the determination of selexipag in bulk and dosage form: A comparative study using different greenness assessment tools. Microchem J. 2023;185:108256. https://doi.org/10.1016/j.microc.2022.108256
7. Amara Babu NL, Koganti K, Palakeeti B, Srinivas KS, Rao KP. Development of an efficient stability-indicating LC–MS/MS method for the analysis of selexipag and characterization of its degradation products. Biomed. Chromatogr. 2021;35(10):e5178.
8. Bhadru B, Rao VV, Vidhyadhara S, Research. Development and validation of bioanalytical method for the quantitative estimation of selexipag in biological matrices using LC-MS/MS. J Pharm Sci. 2019;11(7):2722-7. ISSN:0975-1459

9. Gorumutchu GP, Ratnakaram NR. Oxidative coupling: A tranquil approach for determination of selexipag by visible spectrophotometry. Orient. J. Chem. 2018;34(6):3112. http://dx.doi.org/10.13005/ojc/340656
10. Ceylan B, Tırıs G, Tekkeli SEK, Önal C, Önal A. A novel HPLC method for selexipag in human plasma and application to a pharmacokinetic study. Research Square. 2022. https://doi.org/10.21203/rs.3.rs-1877128/v1
11. Prathyusha SM, Deepti CA, Naik RR, Technology. Development and validated of spectrophotometric methods for the determination of Selexipag (An anti-hypertensive agent). RJPT. 2020;13(3):1346-50. https://doi.org/10.5958/0974-360X.2020.00248.6