Clay R Tynes1, Brad Livingston1, Hetesh Patel2, John J Arnold1. 1. Department of Pharmaceutical, Administrative, and Social Sciences, McWhorter School of Pharmacy, Samford University, Birmingham, Alabama. 2. Department of Pharmacy, Children's of Alabama Health System, Birmingham, Alabama.
Abstract
OBJECTIVES: The purpose of this study was to evaluate the chiral stability of clopidogrel bisulfate in an extemporaneously compounded oral suspension for a period of 60 days. METHODS: A 5 mg/mL oral suspension of clopidogrel bisulfate was prepared from commercially available Plavix tablets. The clopidogrel suspension was then evenly divided between two light-resistant prescription bottles and stored either under refrigeration (4°C) or at room temperature (25°C). Samples were drawn from the stored suspensions immediately after preparation and on days 7, 14, 28, and 60. Samples were subsequently analyzed at each time point by high-performance liquid chromatography using a reversed-phase column, with chemical stability defined as the retention of at least 90% of the initial intact clopidogrel concentration measured. To determine the chiral stability of the suspension, samples were also analyzed by high-performance liquid chromatography using a chiral column to investigate possible enantiomeric inversion. Chiral stability was defined as the retention of at least 90% of the initial concentration of the suspension as the S-enantiomer, the active moiety of Plavix. RESULTS: Regardless of storage conditions, the oral suspension of clopidogrel retained at least 98% of the active S-enantiomer for 60 days after preparation. Compared with the clopidogrel suspension stored in the refrigerator, more chiral inversion was noted in the clopidogrel suspension stored at room temperature. CONCLUSIONS: Our investigation of chiral stability indicates that a 5 mg/mL clopidogrel oral suspension stored under refrigeration and at room temperature maintains chiral stability as the active S-enantiomer.
OBJECTIVES: The purpose of this study was to evaluate the chiral stability of clopidogrel bisulfate in an extemporaneously compounded oral suspension for a period of 60 days. METHODS: A 5 mg/mL oral suspension of clopidogrel bisulfate was prepared from commercially available Plavix tablets. The clopidogrel suspension was then evenly divided between two light-resistant prescription bottles and stored either under refrigeration (4°C) or at room temperature (25°C). Samples were drawn from the stored suspensions immediately after preparation and on days 7, 14, 28, and 60. Samples were subsequently analyzed at each time point by high-performance liquid chromatography using a reversed-phase column, with chemical stability defined as the retention of at least 90% of the initial intact clopidogrel concentration measured. To determine the chiral stability of the suspension, samples were also analyzed by high-performance liquid chromatography using a chiral column to investigate possible enantiomeric inversion. Chiral stability was defined as the retention of at least 90% of the initial concentration of the suspension as the S-enantiomer, the active moiety of Plavix. RESULTS: Regardless of storage conditions, the oral suspension of clopidogrel retained at least 98% of the active S-enantiomer for 60 days after preparation. Compared with the clopidogrel suspension stored in the refrigerator, more chiral inversion was noted in the clopidogrel suspension stored at room temperature. CONCLUSIONS: Our investigation of chiral stability indicates that a 5 mg/mL clopidogrel oral suspension stored under refrigeration and at room temperature maintains chiral stability as the active S-enantiomer.
Authors: Jennifer S Li; Eric Yow; Katherine Y Berezny; Paula M Bokesch; Matsato Takahashi; Thomas P Graham; Stephen P Sanders; Daniel Sidi; Damien Bonnet; Peter Ewert; Lisa K Jennings; Alan D Michelson Journal: Circulation Date: 2008-01-14 Impact factor: 29.690
Authors: M S Rashid Roni; Nicolas M Zahn; Gene T Yocum; Daniel A Webb; Md Yeunus Mian; Michelle J Meyer; Anika S Tylek; James M Cook; Charles W Emala; Douglas C Stafford; Leggy A Arnold Journal: Drug Dev Res Date: 2022-03-04 Impact factor: 5.004