Context: Cisplatin is a highly effective chemotherapeutic agent against many tumors; however, it has potent adverse effects. Zengmian Yiliu granule (ZMYL), a traditional Chinese medicine (TCM) compound, has been clinically used against platinum (Pt)-induced toxicity and to enhance the efficacy of cisplatin. Objective: The study was conducted to investigate the likelihood of potential pharmacokinetics drug-herbs interaction (DHI) between cisplatin and ZMYL. Materials and methods: An improved ICP-MS method combined with ultrafiltration and microwave-assisted digestion was performed to determine the total and free Pt concentrations in rat plasma after intraperitoneal administration of cisplatin (9 mg/kg) or a combined administration with ZMYL (1 g/kg) by gavage. Results: ZMYL produced a potential DHI on the pharmacokinetic parameters of cisplatin, calculated from the total Pt concentration. The clearance rate decreased from 110.52 to 66.12 mLh À1 kg
À1, the mean residence time extended from 63.1 to 164.54 h, the area under the plasma concentration-time curve increased from 86.58 to 152.93 mg h mL
À1, the elimination half-life extended from 48.38 to 126.4 h, and the elimination rate constant decreased from 0.017 to 0.006 h, in the ZMYL combination group (p50.05). In terms of free Pt concentration, the apparent volume of distribution and clearance rate was statistically different (p50.05). The Pt plasma protein binding ratios in the early dose stages were significantly boosted by the coadministration of ZMYL (p50.01). Discussion and conclusion: ZMYL is a potential complementary and alternative medicine for cisplatin chemotherapy. The therapeutic benefits of ZMYL-cisplatin chemotherapy derived from pharmacokinetic interaction needs further investigation.