Development and validation of doxorubicin hydrochloride and doxorubicinol in plasma using liquid chromatography-tandem mass spectrometry

Yahdiana Harahap, Herman Suryadi, Agatha C. Winarti

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Doxorubicin is an anthracycline antibiotic glicoside which has antineoplastic activity and is the most administrated chemotherapy agent to medicate solid tumour in adults including lungs, ovarium, and breast cancer1,2,3. Long term use of this chemotherapy agent is limited because the development of progressive dose-dependent cardiomyopathy which develops irreversibly towards congestive heart failure. The cardiotoxic impact of doxorubicin is highly determined by accumulation of its main metabolite, doxorubicinol4. The aim of this study was to obtain a validated analysis method of doxorubicin and doxorubicinol simultaneously in plasma with hexamethylphosphoramide as the internal standard utilizing liquid chromatography-tandem mass spectrometry. METHODS: Sample preparation was performed by protein precipitation using methanol. The separation was performed using UPLC C-18 BEH (2.1 x 100 mm), 1.7 μm column, 45oC temperature column. The mobile phase consisted of 0.1% acetate acid (eluent A) and acetonitrile (eluent B) at 0.15 ml/min with gradient elution. The detection of the mass was performed on Waters Xevo TQD using ESI positive (+) type MRM for doxorubicin, doxorubicinol, and hexamethylphosphoramide with m/z values: 544.22>361.05; 546.22>363.05; and 180.03>135.16, respectively RESULTS: This method is linear in the range concentration of 1-100 ng/mL for doxorubicin with r value = 0.9963; 0.5-50 ng/mL for doxorubicinol with r value = 0.9977. %Diff and %CV of the assay were less than 20% for LLOQ and less than 15% for other concentration. LLOQ for doxorubicin and doxorubicinol 1.0 ng/mL and 0.5 ng/mL respectively. CONCLUSIONS: This method has successfully fulfilled validation requirement refers to EMEA Guidelines 20115 and FDA guidelines 20186.

Original languageEnglish
Pages (from-to)299-303
Number of pages5
JournalSystematic Reviews in Pharmacy
Volume11
Issue number7
DOIs
Publication statusPublished - Aug 2020

Keywords

  • Cardiotoxicity
  • Doxorubicin
  • Doxorubicinol
  • Hexamethylphosphoramide
  • UHPLC-MSMS

Fingerprint Dive into the research topics of 'Development and validation of doxorubicin hydrochloride and doxorubicinol in plasma using liquid chromatography-tandem mass spectrometry'. Together they form a unique fingerprint.

Cite this