title: Analytical Enantio-Separation of Linagliptin in Linagliptin and Metformin HCl Dosage Forms by Applying Two-Level Factorial Design.
abstract: A novel, stability indicating, reverse phase high-performance liquid chromatography (RP-HPLC) method was developed to determine theS-isomer of linagliptin (LGP) in linagliptin and metformin hydrochloride (MET HCl) tablets (LGP-MET HCl) by implementing design of experiment (DoE), i.e., two-level, full factorial design (2³ + 3 centre points = 11 experiments) to understand the critical method parameters (CMP) and its relation with the critical method attribute (CMA), and to ensure robustness of the method. The separation of theS-isomer, LGP and MET HCl in the presence of their impurities was achieved on Chiralpak®IA-3 (Amylose tris (3, 5-dimethylphenylcarbamate), immobilized on 3 µm silica gel) stationary phase (250 × 4.6 mm, 3 µm) using isocratic elution and detector wavelength at 225 nm with a flow rate of 0.5 mL·min-1, an injection volume of 10 µL with a sample cooler (5 °C) and column oven temperature of 25 °C. Ethanol:Methanol:Monoethanolamine (EtOH:MeOH:MEA) in the ratio of 60:40:0.2v/v/vwas used as a mobile phase. The developed method was validated in accordance with international council for harmonisation (ICH) guidelines and was applied for the estimation of theS-isomer of LGP in LGP-MET HCl tablets. The same method also can be extended for the estimation of theS-isomer in LGP dosage forms.
authors.affiliation: Department of Chemistry, Shivaji University, Kolhapur 416-004, Maharashtra, India. jadhavsb@drreddys.com.|Research and Development, Integrated Product Development, Dr. Reddy's Laboratories Ltd., Bachupally, Hyderabad 500-090, Telangana, India. jadhavsb@drreddys.com.
authors.forename: Sushant B
authors.initials: SB
authors.lastname: Jadhav
authors.affiliation: Department of Chemistry, Shivaji University, Kolhapur 416-004, Maharashtra, India. maners09@gmail.com.
authors.forename: Rahul M
authors.initials: RM
authors.lastname: Mane
authors.affiliation: Research and Development, Integrated Product Development, Dr. Reddy's Laboratories Ltd., Bachupally, Hyderabad 500-090, Telangana, India. kalyanaramanl@drreddys.com.
authors.forename: Kalyanraman L
authors.initials: KL
authors.lastname: Narayanan
authors.affiliation: Department of Chemistry, Shivaji University, Kolhapur 416-004, Maharashtra, India. p_n_bhosale@rediffmail.com.
authors.forename: Popatrao N
authors.initials: PN
authors.lastname: Bhosale
keywords: S-isomer; design of experiments (DoE); development; enantiomer; linagliptin and metformin hydrochloride