title: Improving sensitivity in chiral supercritical fluid chromatography for analysis of active pharmaceutical ingredients.
abstract: Despite its status as the preferred method for routine enantiopurity analysis in pharmaceutical research, supercritical fluid chromatography (SFC) has historically been unsuited for the accurate and precise measurements required for release testing of active pharmaceutical ingredients (APIs) under current good manufacturing processes (cGMPs). Insufficient signal to noise, as compared to HPLC, has heretofore been the major limitation of the chiral SFC approach. We herein describe an investigation into the fundamental limitations and sources of noise in the SFC approach, identifying thermal, electronic, and mechanical sources of noise within the flow cell as key parameters contributing to reduced sensitivity. A variety of instrument modifications are explored, ultimately leading to the development of a new and improved flow cell and other instrument modifications that allow suitable sensitivity and accuracy to carry out GMP release testing for enantiopurity analysis using SFC.
authors.affiliation: Early Development Analytical Research, Department of Process Research, Merck Research Laboratories, RY 801-C101, Rahway, New Jersey 07065, USA. roy_helmy@merck.com
authors.forename: Roy
authors.initials: R
authors.lastname: Helmy
authors.forename: Mirlinda
authors.initials: M
authors.lastname: Biba
authors.forename: Jia
authors.initials: J
authors.lastname: Zang
authors.forename: Bing
authors.initials: B
authors.lastname: Mao
authors.forename: Kimber
authors.initials: K
authors.lastname: Fogelman
authors.forename: Vaso
authors.initials: V
authors.lastname: Vlachos
authors.forename: Paul
authors.initials: P
authors.lastname: Hosek
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Welch
mesh_terms: D002245:Carbon Dioxide; D002845:Chromatography / Q000295:instrumentation / Q000379:methods* / Q000706:statistics & numerical data; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000706:statistics & numerical data; D004867:Equipment Design; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
chemical_list: D004364:Pharmaceutical Preparations; D002245:Carbon Dioxide