Systematic Selection of Internal Standard with Similar Chemical and UV Properties to Drug to Be Quantified in Serum Samples
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This paper describes the selection of an internal standard for the quantification of a model drug in blood samples by a predictive approach based on three retention models for ionizable compounds. The three models are the Abraham’s solvation parameter, simple and improved Log(P) models (P is the partition coefficient between 1-octanol and water). The separation is performed by a Zorbax StableBond ODS column, and acetonitril-(ACN)/water mobile phase (0.1% trifluoroacetic acid, TFA) via a linear gradient elution. The retention times of reference solutes are obtained under the separation conditions, and correlated with their molecular descriptors via linear and nonlinear regression to obtain the model equations for the internal standard prediction. The models are then used to compute the retention of internal standard candidates that possess very similar UV and physical properties to the drug. The final internal standard is chosen by not only the desired retention time, but also the UV and partition properties for the ideal recovery and detection. 4′-aminoacetophenone was finally selected as the internal standard for the quantification.
KeywordsColumn liquid chromatography Ion-pair chromatography Solvation parameter model Retention prediction Log (P) model
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The authors would like to sincerely acknowledge the support of department of Transdermal Drug Delivery, 3M Drug Delivery Systems Division, 3M Company, for this study.
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