Ultrasensitive SERS detection of antitumor drug methotrexate based on modified Ag substrate

Methotrexate (MTX) is a drug with broad-spectrum antitumor activity that is of great importance in therapeutic drug monitoring applications. In this essay, the two-step modified concentrated Ag colloid with the assistance of KF and MgSO₄ was used as the SERS active substrate for the ultrasensitive detection of MTX and its commercial formulations (tablets). It can be found that the two-step modification of the samples is a crucial procedure to remove the by-products in the synthesis of Ag colloid and further concentrate the Ag colloid. Under the optimal detection conditions, the minimum detection concentration of MTX is 1 × 10^-16 mol/L. And, there is a good linear relationship over a wide concentration range of 1 × 10^-16-1 × 10^-6 mol/L. The labelled amounts of the two manufacturers of MTX commercial tablets are in the range of 96.4-104.3% with the RSDs between 1.8% and 3.5% by this method, which are in accordance with the methodological requirements. These results prove that the proposed SERS method exhibits a good reproducibility and ultra-high sensitivity for the detection of the antitumor drug MTX.