PMID- 21682993
OWN - NLM
STAT- MEDLINE
DCOM- 20110916
LR  - 20190513
IS  - 1945-239X (Electronic)
IS  - 0021-9665 (Linking)
VI  - 49
IP  - 6
DP  - 2011
TI  - Quality by design (QbD) based development of a stability indicating HPLC method 
      for drug and impurities.
PG  - 439-46
AB  - In this paper, an application of Quality by Design (QbD) concepts to the 
      development of a stability indicating HPLC method for a complex pain management 
      drug product containing drug substance, two preservatives, and their degradants 
      is described. The QbD approach consisted of (i) developing a full understanding 
      of the intended purpose, (ii) developing predictive solutions, (iii) designing a 
      meaningful system suitability solution that helps to identify failure modes, and 
      (iv) following design of experiments (DOE) approach. The starting method lacked 
      any resolution among drug degradant and preservative oxidative degradant peaks, 
      and peaks for preservative and another drug degradant. The method optimization 
      was accomplished using Fusion AE software (S-Matrix Corporation, Eureka, CA) 
      that follows a DOE approach. Column temperature (50 +/- 5 degrees C), mobile phase buffer 
      pH (2.9 +/- 0.2), initial % acetonitrile (ACN, 2 +/- 1%), and initial hold time (2.5, 
      5, or 10 min) of the HPLC method were simultaneously studied to optimize 
      separation of the unresolved peaks. The optimized HPLC conditions (column 
      temperature of 50 degrees C, buffer pH of 3.1, 3% initial ACN with 2.5 min initial hold) 
      resulted in fully resolved peaks in the two critical pairs. The QbD based method 
      development helped in generating a design space and operating space with 
      knowledge of all method performance characteristics and limitations and 
      successful method robustness within the operating space.
FAU - Karmarkar, S
AU  - Karmarkar S
AD  - Baxter Healthcare Corporation, Technology Park, Round Lake, IL 60073, USA. 
      Shreekant_karmarkar@baxter.com
FAU - Garber, R
AU  - Garber R
FAU - Genchanok, Y
AU  - Genchanok Y
FAU - George, S
AU  - George S
FAU - Yang, X
AU  - Yang X
FAU - Hammond, R
AU  - Hammond R
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Chromatogr Sci
JT  - Journal of chromatographic science
JID - 0173225
RN  - 0 (Acetonitriles)
RN  - Z072SB282N (acetonitrile)
SB  - IM
MH  - Acetonitriles/chemistry
MH  - Chromatography, High Pressure Liquid/*methods
MH  - *Computer-Aided Design
MH  - Drug Contamination
MH  - *Drug Design
MH  - Drug Stability
MH  - Software
MH  - Temperature
EDAT- 2011/06/21 06:00
MHDA- 2011/09/17 06:00
CRDT- 2011/06/21 06:00
PHST- 2011/06/21 06:00 [entrez]
PHST- 2011/06/21 06:00 [pubmed]
PHST- 2011/09/17 06:00 [medline]
AID - 10.1093/chrsci/49.6.439 [doi]
PST - ppublish
SO  - J Chromatogr Sci. 2011;49(6):439-46. doi: 10.1093/chrsci/49.6.439.