title: Determination of Bortezomib in API Samples Using HPLC: Assessment of Enantiomeric and Diastereomeric Impurities.
abstract: A new, normal phase high performance liquid chromatography (NP-HPLC) method was developed for separation of Bortezomib (BZB) enantiomers and quantitative determination of (1S,2R)-enantiomer of BZB in active pharmaceutical ingredient (API) samples. The developed method was validated based on International Conference on Harmonisation (ICH) guidelines and it was proved to be accurate, precise and robust. The obtained resolution (RS) between the enantiomers was more than 2. The calibration curve for (1S,2R)-enantiomer was found to be linear in the concentration range of 0.24-5.36 mg/L with regression coefficient (R2) of 0.9998. Additionally, the limit of detection (LOD) and limit of quantification (LOQ) were 0.052 and 0.16 mg/L, respectively. Also, in this study, a precise, sensitive and robust gradient reversed-phase HPLC (RP-HPLC) method was developed and validated for determination of BZB in API samples. The detector response was linear over the concentration range of 0.26-1110.5 mg/L. The values of R2, LOD and LOQ were 0.9999, 0.084 and 0.25 mg/L, respectively. For both NP-HPLC and RP-HPLC methods, all of the RSD (%) values obtained in the precision study were <1.0%. System suitability parameters in terms of tailing factor (TF), number of theoretical plates (N) and RS were TF < 2.0, N > 2,000 and RS > 2.0. The performance of two common integration methods of valley to valley and drop perpendicular for drawing the baseline between two adjacent peaks were investigated for the determination of diastereomeric impurity (Imp-D) in the BZB-API samples. The results showed that the valley to valley method outperform the drop perpendicular method for calculation of Imp-D peak areas. Therefore, valley to valley method was chosen for peak integration.
authors.affiliation: R&D Department, Quality Control Laboratories, Tofigh Daru Research and Engineering Company, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Kamalzadeh
authors.affiliation: Instrumental Analysis Department, Quality Control Laboratories, Tofigh Daru Research and Engineering Company, Tehran, Iran.
authors.forename: Esmaeil
authors.initials: E
authors.lastname: Babanezhad
authors.affiliation: R&D Department, Quality Control Laboratories, Tofigh Daru Research and Engineering Company, Tehran, Iran.|Instrumental Analysis Department, Quality Control Laboratories, Tofigh Daru Research and Engineering Company, Tehran, Iran.|Young Researchers and Elite Club, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran.|Pharmaceutical Sciences Research Center, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran.
authors.forename: Solmaz
authors.initials: S
authors.lastname: Ghaffari
authors.affiliation: Instrumental Analysis Department, Quality Control Laboratories, Tofigh Daru Research and Engineering Company, Tehran, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Mohseni Ezhiyeh
authors.affiliation: Instrumental Analysis Department, Quality Control Laboratories, Tofigh Daru Research and Engineering Company, Tehran, Iran.
authors.forename: Mahdieh
authors.initials: M
authors.lastname: Mohammadnejad
authors.affiliation: Instrumental Analysis Department, Quality Control Laboratories, Tofigh Daru Research and Engineering Company, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Naghibfar
authors.affiliation: Anticancer Drug Development Department, Tofigh Daru Research and Engineering Company, Tehran, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Bararjanian
authors.affiliation: R&D Department, Quality Control Laboratories, Tofigh Daru Research and Engineering Company, Tehran, Iran.|Chemical Engineering Department, Engineering and Technology Faculty, Sciences and Research Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Attar
mesh_terms: D000069286:Bortezomib / Q000032:analysis* / Q000592:standards; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004340:Drug Contamination; D057230:Limit of Detection; D016014:Linear Models; D015203:Reproducibility of Results; D013237:Stereoisomerism
chemical_list: D000069286:Bortezomib