Simultaneous analysis of acyclovir and its metabolite using hydrophilic interaction liquid chromatography-tandem mass spectrometry.

The antiviral drug acyclovir (ACV) may induce drug-induced neuropsychiatric symptoms as side effects. The detailed pathogenic mechanism remains unclear; however, it is hypothesized that 9-carboxymethoxymethylguanine (CMMG), a metabolite of ACV, is the causative compound. Therefore, the blood concentrations of ACV and CMMG should be analyzed in ACV toxicity studies. However, it is rare to find methods that can sufficiently separate the ACV and CMMG peaks during simultaneous analysis of both compounds. Therefore, we intended to develop a liquid chromatography-tandem mass spectrometry method with improved peak separation of analytes. Samples were deproteinized using methanol/acetonitrile solution (6:4, v/v). Analytes were separated on an InertSustain® Amide column (3 µm, 2.1 mm × 150 mm). The mobile phase consisted of acetonitrile/10 mM ammonium formate (5:95, v/v) (A) and acetonitrile/10 mM ammonium formate (95:5, v/v, pH 5.0) (B) and samples were eluted in the gradient mode. The separation of analytes was satisfactory and the peak shapes were good. Linear regression models weighted 1/x2 were obtained in the range of 0.25-10 µg/mL. The range of quality control (QC) bias was between 3.6% and 19.8%, and the within-run and between-run precisions of QC were within 13.5%. Recovery ranged from 83.6% to 103.7%, but ion suppression was observed. Samples from a patient with ACV encephalopathy were analyzed using this method. The resulting blood ACV and CMMG concentrations were 8.2 and 8.5 µg/mL, respectively. This method, with sufficient separation of ACV and CMMG, proved useful for use in ACV toxicity studies.

Characteristics of Patients Transported by Doctor-Requested Helicopters After Japan's 2011 Nuclear Incident.

OBJECTIVES: This study examined the characteristics of severe patients after the Great East Japan Earthquake in 2011. METHODS: Cases in the Futaba area were extracted using the dispatch database of the doctor helicopter and flight-nurse records from March 11, 2008, till March 10, 2014. The period before March 11, 2011, was defined as 'pre-earthquake' and the period after March 11, 2011, as 'post-earthquake' to compare the recorded data. RESULTS: Of the 128 total recorded cases, 78 were dispatched during the pre-earthquake period and 50 during the post-earthquake period. The number of patients with physical trauma following the earthquake included 4 patients (33.3%) in 2011, 7 patients (43.7%) in 2012, and 13 patients (59.1%) in 2013. However, the increase in number of requests was not statistically significant (P = 0.33). All 4 incidents of physical trauma in 2011, and 3 out of 7 incidents in 2012, occurred at the power plants. A total of 4 incidents occurred at decontamination worksites in 2013. CONCLUSIONS: It is of primary importance for hospitals to anticipate physical trauma cases during the reconstruction phase following a disaster, and develop a system for patients with physical trauma in the short- and long-term.