Stability-Indicating RP-HPLC Method Development and Validation for Eltrombopag Olamine in the Presence of Impurities and Degradation Products. Robustness by Design of Expert Software

Abstract

Background A simple and reliable HPLC method for the determination of impurities in Eltrombopag olamine (ELO) film-coated tablets were not available. At the same time, there was no official monograph reported. The proposed research targeted at development of a stability-indicating method for determining impurities in ELO film coated tablets and drug substances. Objective To develop and validate a simple and effective HPLC method for the determination of impurities in ELO film-coated tablets and drug substances. Method All the impurities were separated using the RP-HPLC system equipped with Zorbax SB-Phenyl 150 mm x 4.6 mm, 3.5 µm, column with UV detection at 230 nm with the flow rate of 1.2 mL/min. The column temperature was maintained at 45 °C. Results The proposed method was validated as per current regulatory guidelines. The coefficient of correlation was found to be > 0.999 for all impurities. The limit of detection and quantification for ELO and all specified impurities was determined. The precision and accuracy were obtained for ELO and their related impurities. Intra and inter-day % RSD values were between 1.22% to 2.04%, and recovery of impurity varied between 93.80 to 103.69%. The stability of standard and sample solutions was established for 24 hrs. Conclusion As per recent guidelines, a stability-indicating method has been developed to determine the impurities in ELO film-coated tablets and drug substances. QbD-based robustness was performed and proved that the method was robust. Highlights The proposed article is the first-ever RP HPLC method for determining impurities in ELO film-coated tablets and drug substances. QbD concept was utilized to verify the method performance.

QbD‐based stability‐indicating liquid chromatography (RP‐HPLC) method for the determination of flurbiprofen in cataplasm

“…The quality by design (QbD) concept is newly, officially introduced by regulatory bodies and the International Conference on Harmonization (ICH) (Dandabattina et al, 2022; ICH, Q14, 2022; Reddy Saddala et al, 2022). The current proposed research considered the guidelines and suggestions from the regulatory bodies and utilized the QbD design of experiments (DoE) approach to study the method robustness (Katakam et al, 2021; Konduru, Gundla, et al, 2022; Konduru, Kowtharapu, & Gundla, 2022; Kowtharapu, Katari, Sandoval, Muchakayala, et al, 2022; Kowtharapu, Katari, Sandoval, Rekulapally, et al, 2022; Kowtharapu, Katari, Surekha, et al, 2022; Muchakayala et al, 2021; Subramanian et al, 2020, 2021).…”

Quality by design tool–evaluated stability‐indicating ultra‐performance liquid chromatography method for the determination of drugs (ritonavir and darunavir) used to treat the human immunodeficiency virus/acquired immunodeficiency syndrome

“…In general, the technique should be enhanced or its robustness should be proven using the quality by design (QbD) approach, according to the present regulatory criteria, which are unambiguous. The robustness of the recently presented strategy was demonstrated using the QbD tool (Dandabattina et al, 2023; Jythesh Kumar et al, 2023; Konduru et al, 2022; Kowtharapu et al, 2022; Vemuri et al, 2022). The design of experiments based on QbD were carried out using Design‐Expert software version 13 (Stat‐Ease, Inc., Minneapolis, MN).…”

Development and Validation of Visible Spectrophotometric Method for Estimation of Eltrombopag Olamine in Bulk and Tablet Dosage Form

“…The development of a basic, precise, reliable, and repetitive Visible Spectrophoto-metric method for the quantification of Eltrombopag Olamine in bulk and in tablet dosage form is described in the current work. According to ICH Guidelines, the developed approach was validated [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27].…”