Abstract
A rapid, simple and single stereo selective high-performance liquid chromatographic (HPLC) method was developed and validated for enantiomers of palonosetron hydrochloride (PALO) and its process related chiral impurities. A computer simulating software was used for the development of chiral method. The developed method was able to separate not only the enantiomers of palonosetron hydrochloride but also its process related chiral impurities within 12 min. The chromatographic separation was carried out by normal phase chromatography using a 3 µm column of cellulose based chiral stationary phase (Chiralcel-OD 250mm × 4.6mm) with a mobile phase comprised of n-hexane: ethanol: methanol: heptafluoro butyric acid: diethyl amine (70:15:15:0.05:0.1, v/v) at a flow rate of 1.0 mL/min. The effects of additive concentration as well as nature of polar organic modifier, flow rate, and temperature on enantioselectivity were investigated. The limit of detection (LOD) and limit of quantification (LOQ) of the palonosetron isomers and its related chiral impurities were found to be in the range 0.06-0.10 µg/mL and 0.14 - 0.24 µg/mL respectively. The method showed excellent linearity (R2 > 0.998) over a range of 0.14 to 1.125 µg/mL. The percentage recovery of the isomers in bulk drug samples ranged from 87.0 to 116.0.
Highlights
Palonosetron hydrochloride [palonosetron hydrochloride (PALO) (3aS, 2S), Comp-1, Figure 1], (3aS)-2-[(S)-1-Azabicyclo [2.2.2] oct-3-yl]-2, 3, 3a, 4, 5, 6-hexahydro-1-oxo-1Hbenz [de] isoquinoline hydrochloride, is a highly selective 5-HT3 receptor antagonist used for the prevention of acute, delayed nausea and vomiting, associated with initial and repeat course of moderately and highly emetogenic cancer chemotherapy [1,2,3,4]
The limit of detection (LOD) and limit of quantification (LOQ) of the palonosetron isomers and its related chiral impurities were found to be in the range 0.06-0.10 μg/mL and 0.14 - 0.24 μg/mL respectively
Palonosetron hydrochloride [PALO (3aS, 2S), Comp-1, Figure 1], (3aS)-2-[(S)-1-Azabicyclo [2.2.2] oct-3-yl]-2, 3, 3a, 4, 5, 6-hexahydro-1-oxo-1Hbenz [de] isoquinoline hydrochloride, is a highly selective 5-HT3 receptor antagonist used for the prevention of acute, delayed nausea and vomiting, associated with initial and repeat course of moderately and highly emetogenic cancer chemotherapy [1,2,3,4]
Summary
Palonosetron hydrochloride [PALO (3aS, 2S), Comp-1, Figure 1], (3aS)-2-[(S)-1-Azabicyclo [2.2.2] oct-3-yl]-2, 3, 3a, 4, 5, 6-hexahydro-1-oxo-1Hbenz [de] isoquinoline hydrochloride, is a highly selective 5-HT3 receptor antagonist used for the prevention of acute, delayed nausea and vomiting, associated with initial and repeat course of moderately and highly emetogenic cancer chemotherapy [1,2,3,4]. The released serotonin activates the 5-HT3 receptors located on vagal afferent nerves to initiate the vomiting reflex. Palonosetron selectively blocks serotonin 5-HT3 receptors reduces the incidence of chemotherapy-induced nausea and vomiting (CINV). Palonosetron hydrochloride contains two stereogenic centers and exists as four stereoisomers: PALO (3aS, 2S), PALO (3aR, 2R), PALO (3aS, 2R), and PALO (3aR, 2S). These isomers may have different pharmacological activities when compared to the therapeutically active molecule. It is necessary to develop an enantiomeric separation method for PALO isomers. A very few analytical methods are available in the literature for the separation of the four enantiomers of PALO
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