Jadhav Sushant B, Mane Rahul M, Narayanan Kalyanraman L, Bhosale Popatrao N
Department of Chemistry, Shivaji University, Kolhapur 416-004, Maharashtra, India.
Research and Development, Integrated Product Development, Dr. Reddy's Laboratories Ltd., Bachupally, Hyderabad 500-090, Telangana, India.
Sci Pharm. 2016 Oct 17;84(4):671-684. doi: 10.3390/scipharm84040671.
A novel, stability indicating, reverse phase high-performance liquid chromatography (RP-HPLC) method was developed to determine the -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 the -isomer, LGP and MET HCl in the presence of their impurities was achieved on Chiralpak IA-3 (), 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, 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 60:40:0.2 // was 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 the -isomer of LGP in LGP-MET HCl tablets. The same method also can be extended for the estimation of the -isomer in LGP dosage forms.
开发了一种新型的、具有稳定性指示功能的反相高效液相色谱（RP-HPLC）方法，通过实施实验设计（DoE），即二水平全因子设计（2³ + 3个中心点 = 11次实验）来测定利格列汀（LGP）和盐酸二甲双胍（MET HCl）片剂（LGP-MET HCl）中LGP的异构体，以了解关键方法参数（CMP）及其与关键方法属性（CMA）的关系，并确保该方法的稳健性。在Chiralpak IA-3（固定在3 µm硅胶上）固定相（250 × 4.6 mm，3 µm）上，使用等度洗脱，检测波长为225 nm，流速为0.5 mL·min，进样体积为10 µL，配备样品冷却器（5 °C），柱温箱温度为25 °C，实现了在存在杂质的情况下异构体、LGP和MET HCl的分离。以60:40:0.2的乙醇:甲醇:单乙醇胺（EtOH:MeOH:MEA）比例作为流动相。所开发的方法按照国际协调理事会（ICH）指南进行了验证，并应用于LGP-MET HCl片剂中LGP异构体的测定。该方法同样可扩展用于LGP剂型中异构体的测定。
