title: Novel Validated RP-HPLC Method for Bendamustine Hydrochloride Based on Ion-pair Chromatography: Application in Determining Infusion Stability and Pharmacokinetics.
abstract: Ion pair chromatography was used for quantifying bendamustine hydrochloride (BH) in its marketed vial. The permissive objective was to investigate time duration for which highly susceptible drug content of the marketed vial remained stable after reconstitution. However, the method could also be used to measure extremely low levels of drug in rat plasma and a pharmacokinetic study was accordingly conducted to further showcase method's applicability. Optimized separation was achieved on C-18 Purospher®STAR (250 mm × 4.6 mm, 5 μm particle size) column. Mobile phase flowing at 1.5 mL/min consisted of 5 mM sodium salt of octane sulfonic acid dissolved in methanol, water and glacial acetic acid (55:45:0.075) maintained at pH 6. Detection was carried out at 233 nm with BH eluting after 7.8 min. Validation parameters were determined as per ICH guidelines. Limit of detection and limit of quantification were found to be 0.1 µg/mL and 0.33 µg/mL, respectively. The recoveries were 98-102% in bulk and 85-91% in plasma. The developed method was specific for BH, and utilized for assessing its short-term stability in physiologic solvents and forced degradation products in acid, base, oxidative, light and temperature induced stress environments.
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute , Lucknow 226031, India.
authors.forename: Yuvraj
authors.initials: Y
authors.lastname: Singh
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute , Lucknow 226031, India.
authors.forename: Anumandla
authors.initials: A
authors.lastname: Chandrashekar
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute , Lucknow 226031, India.
authors.forename: Vivek K
authors.initials: VK
authors.lastname: Pawar
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute , Lucknow 226031, India.
authors.forename: Veeramuthu
authors.initials: V
authors.lastname: Saravanakumar
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute , Lucknow 226031, India.
authors.forename: Jayagopal
authors.initials: J
authors.lastname: Meher
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute , Lucknow 226031, India.
authors.forename: Kavit
authors.initials: K
authors.lastname: Raval
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute , Lucknow 226031, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Singh
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute , Lucknow 226031, India.
authors.forename: R Dinesh
authors.initials: RD
authors.lastname: Kumar
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute , Lucknow 226031, India manish_chourasia@cdri.res.in.
authors.forename: Manish K
authors.initials: MK
authors.lastname: Chourasia
mesh_terms: D000818:Animals; D000069461:Bendamustine Hydrochloride / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D004355:Drug Stability; D005260:Female; D057230:Limit of Detection; D016014:Linear Models; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results
chemical_list: D000069461:Bendamustine Hydrochloride