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.

Development of delayed neurologic sequelae in acute carbon monoxide poisoning cases caused by briquette-based kotatsu: A case-control study.

ABSTRACT: Briquette-based kotatsu, a traditional Japanese heating system, is still used in rural areas and has been linked to the development of acute carbon monoxide (CO) poisoning. This study aimed to investigate the occurrence of delayed neurologic sequelae (DNS) in patients with acute CO poisoning caused by briquette-based kotatsu.This retrospective study included 17 patients treated for acute CO poisoning due to briquette-based kotatsu, between April 2017 and March 2020. Patients were divided into either a sequelae group (3 patients) or a non-sequelae group (14 patients) based on the presence or absence, respectively, of DNS. Demographic data, kotatsu characteristics, clinical findings, and therapies were compared between the 2 groups.Significant differences were noted in patient posture during their initial discovery. Specifically, all non-sequelae patients only had their legs under the kotatsu quilt and all sequelae patients had their entire bodies under the kotatsu quilt (P = .001). There were no statistically significant differences in carbon monoxide levels in hemoglobin (CO-Hb) or the creatine-kinase myocardial band (CK-MB), between the 2 groups; however, troponin-I levels were significantly higher in the sequelae group (P = .026). Abnormal head imaging findings were noted in 2 sequelae-group patients, with a significant difference between the groups (P = .025).We speculate that acute CO poisoning, caused by briquette-based kotatsu, may lead to DNS more frequently in patients in who cover their entire body with the kotatsu quilt and are found in this position. Patients should be warned about the dangers of acute CO poisoning when using briquette-based kotatsu.