Development and validation of GC–MS method for determination of methcathinone and its main metabolite in mice plasma and brain tissue after SPE: Pharmacokinetic and distribution study

Abstract

Only focusing on the plasma levels is inadequate for the full consideration of the physiological disposition of illicit drugs in vivo. Therefore, we conducted the inclusive study on the in vivo dynamic process of intraperitoneal administration of methcathinone (MET), a well-known member of the synthetic cathinone derivatives, which is structurally similar to amphetamine analogs. This study described a validated, selective and sensitive GC–MS method for the simultaneous quantification of MET and its main metabolite, ephedrine (EPD), in the plasma and brain tissue of mice, after solid phase extraction (SPE). Ephedrine-d3 was used as an internal standard (IS). The developed method was validated following US-FDA guidelines within a concentration range of 5–1000 ng/mL for both drugs (r2 > 0.998) in the mice plasma and brain. The recoveries of MET and EPD from the mice plasma and brain ranged from 108.5 to 112.1%. The intra- and inter-day RSDs were ≤ 11.0 %. The proposed method was applied, for the first time, to investigate the pharmacokinetic (PK) and distribution study of MET and EPD following intraperitoneal administration of MET (1.4 mg/kg) to Swiss albino mice. The results exhibited that the Cmax and Tmax of MET in mice plasma was 517.1 ng/mL and 15 min as compared to 3.6 ng/mL and 2 h of EPD. Moreover, MET rapidly passed the blood brain barrier with Cmax of 1444.5 ng/mL achieved at 15 min, whereas, EPD monitored Cmax of 43.6 ng/mL at 4 h in mice brain. The highest concentration of MET in the mice brain followed by plasma was reported, with a necessity to perform more detailed clinical investigations.