In the sentence extracted from biomedical literature, identify all the chemical entities. The required answer format is the same sentence with HTML <span> tags to mark up specific entities. 
### Entity Markup Guides:
Use <span class="chemical"> to denote a chemical.

### Input Text: In the inpatient setting , the frequency of QT interval prolongation with methadone treatment , its dose dependence , and the importance of cofactors such as drug - drug interactions remain unknown .
### Output Text:
In the inpatient setting , the frequency of QT interval prolongation with <span class="chemical">methadone</span> treatment , its dose dependence , and the importance of cofactors such as drug - drug interactions remain unknown . 