The semi-quantitative applications of the Single-probe SCMS methods have been extended to studying drug-resistant cancer cells. The colorectal cancer cells with Irinotecan (Iri) resistance possess elevated unsaturated lipids and cancer stem cell markers, pointing to the upregulation of SCD1 as a key factor in resistance. The findings suggested that inhibiting SCD1 could enhance Iri sensitivity, offering a potential approach to overcoming drug resistance in clinical treatment. More recently, Chen et al. applied SCMS to evaluate the synergistic effects of combining Iri with metformin, an anti-diabetic medicine, in Iri-resistant colorectal cancer cells . The study revealed that metformin could downregulate lipids and fatty acids, suppressing cancer cell metabolism. Combining metformin with Iri further enhanced the suppression of glycosylated ceramide production, a critical component of cancer cell metabolism. These studies demonstrated the utility of SCMS in investigating drug resistance mechanisms and underscored its potential for broader applications in cancer therapy.