Peripheral opioid receptor antagonists and uses thereof

• Main Authors: SZELIGA JAN, FABIAN STEVEN R, SHAH SYED M, BAZHINA NATALIYA, DONATO GEORGE JOSEPH, OFSLAGER CHRISTIAN, LOKHNAUTH JOHN, MEGATI SREENIVASULU, RADEBAUGH GALEN, MELUCCI CHARLES, ZHANG HUYI, PATEL NIKETA, ZHU TIANMIN
• Format: Patent
• Language: English
• Published: 30.04.2014
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

602667 Disclosed is an isolated compound of formula I which is an oxidative impurity found in samples such as (R)-N-methylnaltrexone bromide, wherein: R1 and R2 are each independently aliphatic; and X- is a suitable anion. Also disclosed is a crystalline form of the compound II-1. Further disclosed is a method of determining the amount of a compound of formula II-1 in a sample of (R)-N-methylnaltrexone when the compound of formula II-1 is present, comprising the steps of: (a) providing a sample of (R)-N-methylnaltrexone bromide; (b) performing LC/MS or HPLC analysis of the sample of (R)-N-methylnaltrexone bromide; and (c) determining the amount of the compound of formula II-1 in the sample of (R)-N-methylnaltrexone bromide. Additionally disclosed is a kit comprising a compound of formula I or II-1; and the kit further comprises one or more reference standards of (R)-N-methylnaltrexone bromide, and/or Impurity B, Impurity C, Impurity D, Impurity E, Impurity F, Impurity G, Impurity H, and Impurity I (as defined herein).