Improving sensitivity in chiral supercritical fluid chromatography for analysis of active pharmaceutical ingredients.
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.
Helmy
Roy
R
Early Development Analytical Research, Department of Process Research, Merck Research Laboratories, RY 801-C101, Rahway, New Jersey 07065, USA. roy_helmy@merck.com
Biba
Mirlinda
M
Zang
Jia
J
Mao
Bing
B
Fogelman
Kimber
K
Vlachos
Vaso
V
Hosek
Paul
P
Welch
Christopher J
CJ
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
D004364:Pharmaceutical Preparations; D002245:Carbon Dioxide