Jorge Smith (Presenter)
Shimadzu Corporation
Authorship: Jorge Smith 1, Miho Kawashima 2, Yoshihiro Hayakawa 2, Taku Tsukamoto 2, Masafumi Kikuchi 3, Masaki Tanaka 3, Shinya Takasaki 3, Hiroaki Yamaguchi 3, Nariyasu Mano 3
1 Shimadzu Scientific Instruments Inc., Columbia, MD, USA, 2 Shimadzu Corporation, Kyoto, Japan, 3 Tohoku University Hospital, Sendai, Japan
| Short Abstract In this paper, we introduce four research use only LC/MS/MS methods for therapeutic drug monitoring (TDM), mycophenolic acid, sunitinib and axitinib, voriconazole, itraconazole, using a mobile phase switching system. With an open access user interface software (Open Solution QuantAnalytics, Shimadzu), analysts can start LC/MS/MS measurement quickly only by selecting a method and placing vials in the specified autosampler plate positions and review the data in office as soon as it becomes available on the designated data server. High-throughput LC/MS/MS methods for TDM with a new data acquisition and processing software was developed. |
Long Abstract
*Introduction
In this paper, we introduce four research use only LC/MS/MS methods for therapeutic drug monitoring (TDM), mycophenolic acid, sunitinib and axitinib, voriconazole, itraconazole. TDM is indispensable for managing drug dosage based on the drug concentration in blood in order to conduct a rational and efficient drug therapy. Liquid chromatography coupled with tandem quadrupole mass spectrometry (LC/MS/MS) is increasingly used in TDM because it can perform selective and sensitive analysis by simple sample pretreatment. In the field of TDM, it is necessary to measure the specimen such as plasma or serum quickly after suitable pretreatment and report the precise result. LC/MS/MS system with a simple and user-friendly interface can provide a streamlined workflow and reduce the load of analysts. We developed high-throughput LC/MS/MS methods for TDM with a new data acquisition and processing software.
*Method
For each compound, more than five calibration standards and three QC samples were prepared. Samples were precipitated in a simple way of deproteination using organic solvent such as methanol or acetonitrile. The resulting supernatant was diluted or dilectly injected into LC/MS/MS without filtration. For LC/MS/MS analysis, a LCMS-8050 triple quadrupole mass spectrometer coupled to a Nexera X2 UHPLC system with mobile phase switching unit (Shimadzu corporation, Japan) was used. In all the methods, the compounds were separated by a reversed phase mode using a common column, Shim-pack GIS (Shimadzu corporation, Japan). All data acquisition and processing were performed by Open Solution QuantAnalytics (Shimadzu corporation, Japan), a software package for acquiring and reviewing quantitative LC/MS/MS data with ease.
*Results and Discussion
Since a common column was used through all the method and a mobile phase switching unit was installed to UHPLC system, there is no need to change the column and mobile phase manually for the method of target compound. Open Solution QuantAnalytics software enables users to submit sample and set the LC/MS/MS condition easily and quickly. Users can start LC/MS/MS measurement only by selecting a predefined method and placing sample vials in the specified autosampler plate positions. The resulting data can be reviewed in office as soon as it becomes available on the designated data server. This system enables easy and quick data acquisition without troublesome operation such as changing a column or mobile phase.
Concentrations of standard solutions in plasma of each compound were 0.2-20 ug/mL for mycophenolic acid, 3-300 ug/mL for sunitinib, 0.3-30 ug/mL for axitinib, 0.1-10 ug/mL for voriconazole, 10-1000 ug/mL for itraconazole and 10-1000 ug/mL for hydroxy-itraconazole. In all the methods, determination coefficient (r2) of calibration curves was larger than 0.995, the precision (n=6) was within 15% RSD, and the accuracy (n=6) was within 80-120%. Excellent linearity, accuracy and precision were obtained within a specific concentration range. All the methods took less than 5 minutes per one LC/MS/MS analysis, including column rinsing.
*Conclusion
・The combination of the Open Solution QuantAnalytics software and LC/MS/MS system with mobile phase switching unit enables easy sample submission and efficient data acquisition. The user only describes the vial position of samples, chooses a predefined method and the resulting data can be reviewed in office as soon as it becomes available on the designated data server.
・Saving time and effort for changing system conditions among each target compounds was achieved with mobile phase switching system and high through-put methods using a common column.
References & Acknowledgements:
| Description | Y/N | Source |
| Grants | no | |
| Salary | yes | Shimadzu corporation |
| Board Member | no | |
| Stock | no | |
| Expenses | no |
IP Royalty: no
| Planning to mention or discuss specific products or technology of the company(ies) listed above: | yes |