Format

Send to

Choose Destination
J Pharm Biomed Anal. 2017 Nov 30;146:195-200. doi: 10.1016/j.jpba.2017.08.029. Epub 2017 Aug 31.

Development and validation of a liquid chromatography-tandem mass spectrometry method for pharmacokinetic study of TM-53, a novel transcriptional coactivator with PDZ-binding motif (TAZ) modulator.

Author information

1
Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology (KRICT), 141, Gajeong-ro, Yuseong-gu, Daejeon, Republic of Korea; College of Pharmacy, Chungbuk National University, 194-31 Osongsaengmyeong 1-ro, Osong-eup, Heungduk-gu, Cheongju, Chungbuk 361-951, Republic of Korea.
2
Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology (KRICT), 141, Gajeong-ro, Yuseong-gu, Daejeon, Republic of Korea.
3
College of Pharmacy, Chungbuk National University, 194-31 Osongsaengmyeong 1-ro, Osong-eup, Heungduk-gu, Cheongju, Chungbuk 361-951, Republic of Korea.
4
Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology (KRICT), 141, Gajeong-ro, Yuseong-gu, Daejeon, Republic of Korea; Department of Medicinal Chemistry and Pharmacology, University of Science & Technology, 141, Gajeong-ro, Yuseong-gu, Daejeon, Republic of Korea.
5
Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology (KRICT), 141, Gajeong-ro, Yuseong-gu, Daejeon, Republic of Korea; Department of Medicinal Chemistry and Pharmacology, University of Science & Technology, 141, Gajeong-ro, Yuseong-gu, Daejeon, Republic of Korea. Electronic address: sahn@krict.re.kr.

Abstract

Transcriptional coactivator with PDZ-binding motif (TAZ) is considered an attractive target for osteoporosis, obesity, and muscle regeneration. TM-53, a promising TAZ modulator, was recently introduced, and here, we developed a rapid, precise, and reliable analytical method for TM-53 and characterized its pharmacokinetic properties in rat plasma. The hybrid triple quadrupole/linear ion trap coupled to liquid chromatography method was developed and validated to quantify TM-53. Additionally, TM-53 concentrations in plasma were analyzed, and its pharmacokinetic parameters were calculated by non-compartmental analysis. Multiple reaction monitoring at m/z 569.4→207.1 showed the most sensitive signals for TM-53, and the linear scope of the standard curve was between 1.5ng/mL and 500ng/mL. The intra- and inter-day precisions of the quality control samples were <15%, and their accuracies were ranged from 86.2% to 111.0%. Furthermore, the matrix effects, extraction recoveries, and process efficiencies of this analytical method for evaluating TM-53 in rat plasma were 99.1%, 99.9%, and 99.1% respectively. In short- and long-term stability studies, TM-53 showed good stability under frozen conditions, but TM-53 hydrolysis in the plasma matrix was observed following storage at room temperature. This analytical method was successfully applied for pharmacokinetic analysis of TM-53 in rat plasma and demonstrated excellent sensitivity, selectivity, precision, and accuracy. These data indicated that this method can be applied for further preclinical studies of TM-53.

KEYWORDS:

LC–MS/MS; Method validation; Pharmacokinetic study; TM-53; Transcriptional coactivator with PDZ-binding motif

PMID:
28886519
DOI:
10.1016/j.jpba.2017.08.029
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center