Development and multicenter validation of an LC-MS-based bioanalytical method for antisense therapeutics.
Bioanalysis
; 14(18): 1213-1227, 2022 Sep.
Article
in En
| MEDLINE
| ID: mdl-36408704
ABSTRACT
Background:
Many bioanalytical methods for antisense oligonucleotides (ASOs) using LC-MS have been reported. However, no data have been available on the reproducibility and robustness of a single bioanalytical method for ASOs. As such, in the current study, we evaluated the reproducibility and robustness of LC-MS-based bioanalytical methods for ASOs in multiple laboratories. Methods/Results:
Seven independent laboratories were included in this study. Mipomersen was measured by ion-pairing LC-MS (IP-LC-MS) as a model ASO using different LC-MS. The validation results of calibration curve, accuracy, precision and selectivity met the criteria of conventional bioanalytical method validation guidelines using LC/GC-MS for drugs in all laboratories. Meanwhile, carryover (>20%) was detected in three laboratories.Conclusion:
We first demonstrated the multicenter-validated IP-LC-MS bioanalytical method for ASOs. Our data showed that the method was sensitive, robust and reproducible. However, the occurrence of carryover should be carefully monitored in its future application.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Biological Therapy
/
Tandem Mass Spectrometry
Type of study:
Clinical_trials
/
Prognostic_studies
Language:
En
Journal:
Bioanalysis
Year:
2022
Type:
Article
Affiliation country:
Japan