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.

Direct and Real-Time Quantification Of Bortezomib Release From Alginate Microparticles Using Boron (11B) Nuclear Magnetic Resonance Spectroscopy

“…The method’s LOD and LOQ were 0.72 mg/mL (1.87 mM) and 2.17 mg/mL (5.65 mM), respectively. These values were significantly higher than values reported for UV spectroscopy (LOD = 0.099 μg/mL and LOQ = 0.301 μg/mL) and HPLC (LOD = 0.084 μg/mL and LOQ = 0.25 μg/mL) methods of BTZ. Nonetheless, the LOD and LOQ values obtained were consistent with the range of other qNMR methods reported in the field of pharmaceutical research. , In general, qNMR methods have a lower sensitivity compared to other analytical methods, such as UV spectroscopy and HPLC.…”

N-2-Hydroxypropylmethacrylamide–Polycaprolactone Polymeric Micelles in Co-delivery of Proteasome Inhibitor and Polyphenol: Exploration of Synergism or Antagonism

“…The flow rate and temperature were maintained at 1.0 mL/min and 25 °C, respectively. The area under the curve of the samples was analyzed at 270 nm . CFA content was analyzed by using methanol+TFA (trifluoroacetic acid)/water+TFA (70:30) as a mobile phase with a flow rate of 1 mL/min.…”

“…The area under the curve of the samples was analyzed at 270 nm. 27 CFA content was analyzed by using methanol+TFA (trifluoroacetic acid)/water+TFA (70:30) as a mobile phase with a flow rate of 1 mL/min. The λ max used for CFA was 280 nm.…”

Sialic Acid Engineered Prodrug Nanoparticles for Codelivery of Bortezomib and Selenium in Tumor Bearing Mice

“…The area under the curve for samples were determined at a wavelength of 270 nm. 38 5.6. pH-Dependent in Vitro Release Profile. The release profile of freshly prepared samples; BSAL-HP prodrug conjugate, Se_BSAL-HP prodrug NPs was compared with BTZ at both normal physiological pH (7.4) and acidic pH (5.6), 37 °C.…”