- 著者
- Toshimasa TOYO’OKA
- 出版者
- (社)日本分析化学会
- 雑誌
- Analytical Sciences (ISSN:09106340)
- 巻号頁・発行日
- vol.33, no.5, pp.555-564, 2017-05-10 (Released:2017-05-10)
- 参考文献数
- 91
- 被引用文献数
- 40
Liquid chromatography coupled with mass spectrometry (LC-MS) is one of the most prominent analytical techniques due to its inherent selectivity and sensitivity. LC-MS is currently the first choice for high-throughput bioanalysis due to the advancements in MS instruments and the analytical software. Based on this situation, we are developing various types of derivatization reagents, including chiral reagents for MS and/or MS/MS detection. These developed reagents are adopted for the detection of biomarker candidates related to diseases. The biomarker candidates include not only achiral molecules, but also chiral ones. Although determining the already-identified chiral molecules is relative easy, it is very difficult to identify and/or determine unknown enantiomer(s) in real samples. To solve this difficulty, we proposed a new strategy to identify unknown enantiomeric biomarkers related to diseases. This review paper deals with the development of derivatization reagents for amines and carboxylic acids in LC-MS analysis and their application to bioanalysis.
- 著者
- Sae SOTOMATSU Tomohiro YAMADA Hajime MIZUNO Hideki HAYASHI Toshimasa TOYO’OKA Kenichiro TODOROKI
- 出版者
- The Society for Chromatographic Sciences
- 雑誌
- CHROMATOGRAPHY (ISSN:13428284)
- 巻号頁・発行日
- pp.2019.013, (Released:2019-06-21)
- 参考文献数
- 16
- 被引用文献数
- 6
To construct liquid chromatography (LC)-based bioanalytical method for therapeutic monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs), twelve commercially available therapeutic mAbs and one ADC were chemically reduced, and the generated fragments were analyzed by high-temperature reversed-phase LC. For most therapeutic mAbs, single peaks of light and heavy chains were detected, indicating a possibility of homogeneous LC analysis using light chains. However, characteristic fragmentations were observed in infliximab, pembrolizumab, ramucirumab, and trastuzumab emtansine. We also performed a simple validation using the fragmented light chains for the bioanalysis of bevacizumab. The limit of detection (LOD) and limit of quantification (LOQ) of bevacizumab were 0.63 and 2.10 µg/mL, respectively, with dithiothreitol reduction, and 0.74 and 2.48 µg/mL, respectively, with tris (2-carboxyethyl) phosphine reduction. These results indicate that both the reductants confer sufficient linearity, LOQ, and LOD for the light chain analysis of bevacizumab. Thus, this method, combined with affinity purification, can be used for the bioanalysis of bevacizumab.
- 著者
- Kenichiro TODOROKI Yuto KUDOH Misuzu NAKAMURA Yuki SHIMIZU Takamitsu SASAKI Hideyuki OTSUKI Keisuke WADA Jun Zhe MIN Hajime MIZUNO Kouichi YOSHINARI Toshimasa TOYO’OKA
- 出版者
- The Japan Society for Analytical Chemistry
- 雑誌
- Analytical Sciences (ISSN:09106340)
- 巻号頁・発行日
- pp.18SCP05, (Released:2018-07-20)
- 被引用文献数
- 6
- 著者
- Kenichiro TODOROKI Tomohiro YAMADA Hajime MIZUNO Toshimasa TOYO’OKA
- 出版者
- The Japan Society for Analytical Chemistry
- 雑誌
- Analytical Sciences (ISSN:09106340)
- 巻号頁・発行日
- vol.34, no.4, pp.397-406, 2018-04-10 (Released:2018-04-10)
- 参考文献数
- 74
- 被引用文献数
- 26
The increase in the use of therapeutic monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) has made the detailed bioanalysis of these drugs essential not only for planning optimal therapeutic programs for clinical practice, but also for evaluating the biological equivalencies in the development of other biosimilars. The ligand binding assays that are widely in use now are being replaced rapidly by the highly accurate, sensitive, and selective analytical method using a mass spectrometer. This review will discuss the progress in and challenges observed during the development of a mass spectrometry-based bioanalytical method for therapeutic mAbs and ADCs.
- 著者
- Toshimasa Toyo’oka Ruri Kikura-Hanajiri
- 出版者
- 公益社団法人日本薬学会
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.63, no.10, pp.762-769, 2015-10-01 (Released:2015-10-01)
- 参考文献数
- 27
- 被引用文献数
- 2 22
A reliable method using supercritical fluid chromatography with mass spectrometry (SFC-MS) was developed for cannabinoids using compressed carbon dioxide (CO2) and methanol as the mobile-phase. The cannabinoids, i.e., cannabicyclohexanol (CCH: cis-isomer), trans-CCH, 5-(1,1-dimethylheptyl)-2-[(1R,3S)-3-hydroxycyclohexyl]-phenol (CP-47497), 5-(1,1-dimethylheptyl)-2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-phenol (CP-55940), 3-(1,1′-dimethylheptyl)-6aR,7,10,10aR-tetrahydro-1-hydroxy-6,6-dimethyl-6H-dibenzo[b,d]pyran-9-methanol (HU-210), 2-[1R-3-methyl-6R-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol (CBD), (1-pentyl-1H-indol-3-yl)-1-naphthalenyl-methanone (JWH-018), (1-butyl-1H-indol-3-yl)-1-naphthalenyl-methanone (JWH-073) and 1-(1-pentyl-1H-indol-3-yl)-2-(2-methoxyphenyl)-ethanone (JWH-250), were determined within 12 min using a conventional column (2-EP) for SFC. Furthermore, two optical isomers of CCH and trans-CCH were completely and rapidly separated by a chiral stationary phase column (AMY1). A highly sensitive detection (0.002–3.75 ppb) was also obtained by these methods using 2-EP and AMY1 columns. These methods were applied to the qualitative and quantitative determination of cannabinoids in dried plant products. Although the concentration and species were different in the products, JWH-018, JWH-073 and CCH, including the cis-isomer, trans-isomer and the optical isomers, were detected in the products. Therefore, the proposed SFC-MS method seems to be useful as an alternative method to GC-MS and LC-MS for illegal drugs, such as cannabinoids.