Determination of etomidate and etomidate acid in hair using liquid chromatography-tandem mass spectrometry.

Etomidate, with efficacy similar to that of propofol, has been used as a propofol substitute because propofol is a designated narcotic drug, and an increase in the frequency of illegal distribution and misuse has been reported in Korea. Previous analytical studies on etomidate used blood and urine. For long-term use and timing estimation, a method for etomidate analysis using hair should be developed. Therefore, in this study, an analytical method using LC-MS/MS was developed to determine etomidate and its major metabolite in hair. Human hair samples were segmented after washing to eliminate possible contaminants on the hair and stirred with methanol. The LC-MS/MS conditions were optimized, and the chromatographic separation time was 10 min. Selectivity, linearity, limit of detection, limit of quantification, precision, accuracy, recovery, process efficiency, matrix effect, and stability were evaluated to validate the analytical method. The calibration curves ranged from 0.25 to 50 pg/mg for etomidate and 2-250 pg/mg for etomidate acid; the coefficients of determination were higher than 0.997. The intra- and inter-assay precision results for all the compounds were <15% and satisfied at recovery, process efficiency, matrix effect, and stability. In addition, this method was applied to the hair of 4 rats which are administered with etomidate to evaluate. The etomidate concentrations in the rat hair ranged from 2.60 to 8.50 pg/mg, and the etomidate acid concentrations were 2.06-7.13 pg/mg. Thus, this method can be used as basic data for monitoring etomidate in hair.

Efficacy and safety of epirubicin and etoposide combination chemotherapy in advanced hepatocellular carcinoma: a retrospective analysis.

BACKGROUND AND AIM: Systemic treatments of advanced hepatocellular carcinoma (AHCC) have offered marginal clinical benefits. Recently, Italian investigators reported that etoposide and epirubicin combination (EE) chemotherapy was highly active against AHCC, with a response rate of 39% and a median overall survival (OS) of 10 months. We report our efficacy and safety results of EE in clinical practice. METHODS: Between December 1999 and October 2005, 35 patients with AHCC and fitting the preset eligibility criteria were treated with EE. Twenty-eight patients (80%) had liver disease associated with hepatitis B virus (HBV) and 26 (74%) had a prior history of transarterial chemoembolization (TACE) using cisplatin. The EE chemotherapy consisted of epirubicin 40 mg/m(2) on day 1 and etoposide 120 mg/m(2) on days 1, 3 and 5 every 4 weeks. RESULTS: A total of 102 chemotherapy cycles were administered, with a median of two cycles per patient (range one to eight cycles). Two patients had a partial response and nine had stable disease, with a tumor control rate of 32% (95% CI 17-48). The median progression-free survival (PFS) was 2.1 months (95% CI 1.8-2.4) and the median OS was 6.4 months (95% CI 4.4-8.5). There was a tendency toward improved PFS in patients seronegative for HBsAg and peritoneal seeding (P = 0.06 and P = 0.054, respectively). Overall survival was significantly better in patients without HBsAg and Cancer Liver Italian Program (CLIP) score 0-1 (P = 0.024 and P = 0.033, respectively). The main toxicities were hematological events, including grade 3/4 neutropenia in 29% and febrile neutropenia in 11% of patients. CONCLUSION: Treatment with EE showed minimal antitumor activity with acceptable toxicity in HBV-associated AHCC, especially in patients pretreated with TACE.