title: Stability studies of potent opioid analgesic, morphine-6-O-sulfate in various buffers and biological matrices by HPLC-DAD analysis.
abstract: The 6-O-sulfate ester of morphine (M6S) has previously been shown to be an analgesic with greater potency and fewer side effects than morphine. However, being a sulfate ester derivative of morphine, the question exists as to whether this compound is stable in biological fluids and tissues with regard to pH- and esterase-mediated degradation. To date, no studies have focused on the stability profile of M6S across the physiologically relevant pH range of 1.2-7.4. In addition, the stability of M6S is not known in rat plasma and rat brain homogenate, or in simulated rat gastric and intestinal fluids. This study determines the stability profile of M6S (utilized as the sodium salt) and demonstrates that M6S is highly stable and resilient to either enzymatic- or pH-dependent hydrolysis in vitro.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Jai Shankar K
authors.initials: JSK
authors.lastname: Yadlapalli
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Zaineb A F
authors.initials: ZAF
authors.lastname: Albayati
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Narasimha R
authors.initials: NR
authors.lastname: Penthala
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Howard P
authors.initials: HP
authors.lastname: Hendrickson
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Peter A
authors.identifier: http://orcid.org/0000-0002-1312-6150
authors.initials: PA
authors.lastname: Crooks
mesh_terms: D000701:Analgesics, Opioid / Q000032:analysis* / Q000097:blood / Q000737:chemistry*; D000818:Animals; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005750:Gastric Juice / Q000737:chemistry; D006801:Humans; D007419:Intestinal Secretions / Q000737:chemistry; D016014:Linear Models; D008297:Male; D008954:Models, Biological; D009022:Morphine Derivatives / Q000032:analysis* / Q000097:blood / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000701:Analgesics, Opioid; D009022:Morphine Derivatives; C572396:morphine-6-O-sulfate
keywords: brain homogenate; morphine-6-O-sulfate; rat plasma; simulated gastric and intestinal fluids; stability; various pH buffers