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ChromSword reduces HPLC method development time for new drugs
By Masatoshi Karashima
Analytical Development Laboratories, Takeda Pharmaceutical Company Limited
In the past, development of HPLC methods for pharmaceutical products relied on trial and error supported by researchers’ past experience and intuition. The increased speed of drug development and the large number of parallel research projects now requires us to develop methods much more quickly. This need led us to try ChromSword software for automated method development.
ChromSword, provided by an Agilent partner, predicts the best separation conditions for HPLC analyses such as chromatography of drug impurities.[1] It can be used in both offline and online modes. The offline mode lets researchers find optimum conditions by entering structural formulae and results of preliminary experiments; the online mode allows the HPLC system itself to optimize the methods for separation by calculating analytical conditions and actually performing experiments. We will be able to streamline our research process by employing appropriate features of ChromSword for each drug development phase. Table 1 shows our tentative plan to do this.
Initial Phase  |
Preclinical |
Phase I – II |
Phase III – NDA  |
- Restriction of pharmaceutical substances
- Insufficient batch history
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- Procurement of pharmaceutical substances
- Forced degradation study
- Discussion on the possibility of pharmaceutical formulation
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- Safety test
- Accumulation of batch history
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- Determination of the structure of analog
- Development of the combination of drugs
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Offline (structure model)
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Offline (polynomial model)
|
Online (screening)
|
Offline (structure model)
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Table 1. Planned use of ChromSword features for each phase of pharmaceutical development.
Excellent correlation between simulation and actual separation
We are currently using ChromSword to develop separation and quantitation methods for drug analogs. We used the offline mode of ChromSword to develop a method for Compound A, which was in the initial phase of drug development. First, we determined a tentative gradient pattern based on basic physical characteristics (for example, UV absorption, pKa, and solubility), and information on the structural formulae of analogs that could be expected from the chemical structure of Compound A.
After obtaining the compound, we ran two preliminary experiments, and optimized the proportion of organic solvent based on the offline mode’s polynomial model. We observed an excellent match between the simulation and the actual measurement (Figure 1).
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Figure 1. The ChromSword prediction correlated well with the observed separation. (Click here to see this image larger.)
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Available from an Agilent partner
Based on these results, ChromSword shows great promise for accelerating our method development. If you want to try this product, note that Agilent has partnered with The ChromSword Group to provide ChromSword Auto 3.5. It is compatible with Agilent 1100 Series, 1200 Series, and 1200 Series Rapid Resolution LCs, with either Agilent ChemStation or Agilent EZChrom Elite data systems. ChromSword also integrates with the Agilent 1200 Series LC Method Development Solution, for fully automated optimization of separation parameters. For more information, visit the ChromSword product page, or talk with your Agilent Representative.
Reference
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E. F. Hewitt, P. Lukulay, and S. Galushko, “Implementation of a rapid and automated high performance liquid chromatography method development strategy for pharmaceutical drug candidates,” J. Chromatogr. A, 1107, 79-87, 2006.
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