Doxorubicinol

• CAS: 54193-28-1
• Catalog Number: ACM54193281
• Category: Main Products
• Molecular Weight: 545.54
• Molecular Formula: C27H31NO11
• Synonyms: Adriamycinol
• Appearance: Dark Red to Black Solid

Case Study

Doxorubicinol Impairs Excitation-Contraction Coupling in Cardiac Myocytes

Wang G-X, et al. European Journal of Pharmacology, 2001, 423(2-3), 99-107.

Doxorubicinol, the primary metabolite of the anticancer drug doxorubicin, has been implicated in the cardiotoxicity associated with doxorubicin treatment. This study investigated its acute effects on excitation-contraction coupling in isolated guinea pig ventricular myocytes using whole-cell patch-clamp, fura-2 fluorescence, and cell-edge tracking techniques. Intracellular administration of doxorubicinol (10 μM) for 15-20 minutes resulted in a 25% reduction in action potential duration (APD) and a 31% decrease in cell shortening, contrasting with doxorubicin, which prolonged APD and enhanced contractility. The APD reduction was attributed to an increased delayed rectifier K+ current, while neither the inward rectifier K+ current nor the L-type Ca2+ current was affected. Additionally, doxorubicinol lowered the peak Ca2+ transient by 23%, independent of APD shortening, indicating a direct impairment in calcium handling. Both doxorubicin and doxorubicinol significantly delayed contraction and Ca2+ transient kinetics, suggesting sarcoplasmic reticulum dysfunction. These findings highlight doxorubicinol's detrimental role in cardiac excitation-contraction coupling, potentially exacerbating doxorubicin-induced cardiotoxicity through impaired Ca2+ homeostasis and contractile dysfunction.

LC-MS/MS Quantification of Doxorubicinol in Rat Plasma for Pharmacokinetic Studies

Liu Y, et al. Talanta, 2008, 74(4), 887-895.

A highly sensitive and validated LC-MS/MS method was developed for the precise quantification of doxorubicinol, the active metabolite of pegylated liposomal doxorubicin, in rat plasma. The method employed Triton X-100 for immediate liposome dispersion, followed by methanol:acetone protein precipitation in the presence of zinc sulfate (70% w/v) to enhance analyte recovery. The separation was achieved using a pentafluorophenylpropyl HPLC column, with daunorubicin as the internal standard. Positive turbo-ion spray ionization was utilized in MRM mode, ensuring high specificity. The validated concentration range for doxorubicinol was 0.05-20.0 ng/mL, allowing for trace-level detection with minimal interference from doxorubicin. The method demonstrated excellent accuracy (85-110%) and precision (CV <14%), with no matrix effects across six different plasma lots. Notably, autosampler carryover was significantly reduced from 285% to 10.5% by optimizing valve washing cycles. This method was successfully applied in a pharmacokinetic study, revealing that the mean AUC of doxorubicinol was only 0.011% of doxorubicin, confirming its limited systemic exposure after a single-dose administration of Stealth-49 liposomal doxorubicin HCl. These findings underscore the effectiveness of LC-MS/MS in quantifying doxorubicinol for pharmacokinetic profiling and drug metabolism studies.

Doxorubicinol Is Used for Chemiluminescence-Based Pharmacokinetic Profiling in Rat Plasma

Ahmed S, et al. Talanta, 2009, 78(1), 94-100.

Doxorubicinol (DXR-ol), the major metabolite of the anthracycline anticancer agent doxorubicin (DXR), plays a critical role in evaluating the pharmacokinetic behavior and cardiotoxic potential of DXR. A highly sensitive and selective analytical method has been established for the quantitative determination of DXR-ol in rat plasma, leveraging a peroxyoxalate chemiluminescence (PO-CL) detection system following high-performance liquid chromatography (HPLC). The methodology utilizes the intrinsic photosensitizing properties of DXR-ol, a fluorescent quinone, to initiate hydrogen peroxide generation via a photosensitization reaction under aerobic conditions in the presence of ethanol as a hydrogen atom donor. Subsequent reaction of hydrogen peroxide with aryloxalate in the post-column stream triggers a PO-CL reaction, allowing the ultrasensitive detection of DXR-ol and its parent compound. Chromatographic separation was achieved isocratically using an ODS column within a rapid 15-minute runtime. The method exhibits femtomolar-level detection limits (3.8 fmol for DXR-ol), making it especially valuable for bioanalytical applications requiring the monitoring of trace levels in complex biological matrices. A minimal sample volume (50 μL) and straightforward methanol-based protein precipitation step further enhance the method's practicality for preclinical pharmacokinetic studies.

Custom Q&A

What is the molecular formula of doxorubicinol?

The molecular formula of doxorubicinol is C27H31NO11.

What are the synonyms for doxorubicinol?

The synonyms for doxorubicinol are Adriamycinol, 54193-28-1, and 13-Dihydrodoxorubicin.

What is the molecular weight of doxorubicinol?

The molecular weight of doxorubicinol is 545.5 g/mol.

What is the IUPAC name of doxorubicinol?

The IUPAC name of doxorubicinol is (7S,9S)-7-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-9-[(1S)-1,2-dihydroxyethyl]-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione.

What is the InChI of doxorubicinol?

The InChI of doxorubicinol is InChI=1S/C27H31NO11/c1-10-22(31)13(28)6-17(38-10)39-15-8-27(36,16(30)9-29)7-12-19(15)26(35)21-20(24(12)33)23(32)11-4-3-5-14(37-2)18(11)25(21)34/h3-5,10,13,15-17,22,29-31,33,35-36H,6-9,28H2,1-2H3/t10-,13-,15-,16-,17-,22+,27-/m0/s1.

What is the InChIKey of doxorubicinol?

The InChIKey of doxorubicinol is NKZRZOVSJNSBFR-FEMMEMONSA-N.

What is the canonical SMILES of doxorubicinol?

The canonical SMILES of doxorubicinol is CC1C(C(CC(O1)OC2CC(CC3=C2C(=C4C(=C3O)C(=O)C5=C(C4=O)C(=CC=C5)OC)O)(C(CO)O)O)N)O.

What is the CAS number of doxorubicinol?

The CAS number of doxorubicinol is 54193-28-1.

What is the UNII of doxorubicinol?

The UNII of doxorubicinol is HUH05KI4CF.

What is the ChEMBL ID of doxorubicinol?

The ChEMBL ID of doxorubicinol is CHEMBL3277946.