PMID- 23850937
OWN - NLM
STAT- MEDLINE
DCOM- 20140227
LR  - 20130729
IS  - 1873-264X (Electronic)
IS  - 0731-7085 (Linking)
VI  - 84
DP  - 2013 Oct
TI  - Improved quality-by-design compliant methodology for method development in 
      reversed-phase liquid chromatography.
PG  - 215-23
LID - S0731-7085(13)00263-X [pii]
LID - 10.1016/j.jpba.2013.06.013 [doi]
AB  - A complete strategy dedicated to quality-by-design (QbD) compliant method 
      development using design of experiments (DOE), multiple linear regressions 
      responses modelling and Monte Carlo simulations for error propagation was 
      evaluated for liquid chromatography (LC). The proposed approach includes four 
      main steps: (i) the initial screening of column chemistry, mobile phase pH and 
      organic modifier, (ii) the selectivity optimization through changes in gradient 
      time and mobile phase temperature, (iii) the adaptation of column geometry to 
      reach sufficient resolution, and (iv) the robust resolution optimization and 
      identification of the method design space. This procedure was employed to obtain 
      a complex chromatographic separation of 15 antipsychotic basic drugs, widely 
      prescribed. To fully automate and expedite the QbD method development procedure, 
      short columns packed with sub-2 mum particles were employed, together with a UHPLC 
      system possessing columns and solvents selection valves. Through this example, 
      the possibilities of the proposed QbD method development workflow were exposed 
      and the different steps of the automated strategy were critically discussed. A 
      baseline separation of the mixture of antipsychotic drugs was achieved with an 
      analysis time of less than 15 min and the robustness of the method was 
      demonstrated simultaneously with the method development phase.
CI  - Copyright (c) 2013 Elsevier B.V. All rights reserved.
FAU - Debrus, Benjamin
AU  - Debrus B
AD  - School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 
      Boulevard d'Yvoy 20, 1211 Geneva 4, Switzerland.
FAU - Guillarme, Davy
AU  - Guillarme D
FAU - Rudaz, Serge
AU  - Rudaz S
LA  - eng
PT  - Journal Article
DEP - 20130621
PL  - England
TA  - J Pharm Biomed Anal
JT  - Journal of pharmaceutical and biomedical analysis
JID - 8309336
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Solvents)
SB  - IM
MH  - Antipsychotic Agents/chemistry
MH  - Chromatography, Liquid/*methods
MH  - Chromatography, Reverse-Phase/*methods
MH  - Hydrogen-Ion Concentration
MH  - Research Design
MH  - Software
MH  - Solvents/chemistry
MH  - Temperature
OTO - NOTNLM
OT  - Automated method development
OT  - Computer-assisted method development
OT  - Design space
OT  - Quality by design
OT  - Robustness
EDAT- 2013/07/16 06:00
MHDA- 2014/02/28 06:00
CRDT- 2013/07/16 06:00
PHST- 2013/03/29 00:00 [received]
PHST- 2013/05/31 00:00 [revised]
PHST- 2013/06/06 00:00 [accepted]
PHST- 2013/07/16 06:00 [entrez]
PHST- 2013/07/16 06:00 [pubmed]
PHST- 2014/02/28 06:00 [medline]
AID - S0731-7085(13)00263-X [pii]
AID - 10.1016/j.jpba.2013.06.013 [doi]
PST - ppublish
SO  - J Pharm Biomed Anal. 2013 Oct;84:215-23. doi: 10.1016/j.jpba.2013.06.013. Epub 
      2013 Jun 21.