Yoshihiro Abe

Production of a reactive metabolite of troglitazone by electrochemical oxidation performed in nonaqueous medium.

In order to confirm the existence of reactive metabolites by LC-MS/MS analysis, they should be modified into stable compounds, because some reactive metabolites generated by biotransformation induce drug toxicity; however, they are unstable, with very short lives, and cannot be detected in their intact forms. To overcome these problems, electrochemical oxidation of troglitazone was performed in nonaqueous medium, since such reactive compounds are stable in the absence of water. Troglitazone, an antidiabetic agent, was withdrawn from the market because of serious hepatotoxicity in some patients. It has been considered that one or more reactive metabolites are involved in hepatotoxicity, although the mechanism of the adverse reaction is unclear. Using our method of electrochemical oxidation in nonaqueous medium, we obtained a product of troglitazone derivative that may be a clue to clarify the mechanism of toxicity. The product in the reaction mixture was separated by HPLC without chemical modification and detected using UV and ESI-MS. The mass spectrum of its molecular ion showed that it was an o-quinone methide derivative of troglitazone and identified as a reactive metabolite generated by liver microsome oxidation of the drug. The product was stable over 24 h at room temperature in anhydrous acetonitrile, but it reacted with N-(tert-butoxycarbonyl)-L-cystein methylester to produce an adduct that could be identified by its m/z value. Thus, the method of electrochemical oxidation in nonaqueous medium is considered to be useful to prepare and predict reactive metabolites of drugs that are unstable in aqueous medium or in vivo.

Elucidation of molybdosilicate complexes in the molybdate yellow method by ESI-MS.

The formation of molybdosilicate in the molybdate yellow method is elucidated by ESI-MS. Polymeric silicic acids were hydrolyzed to monomers, and molybdosilicates with a Keggin structure were formed. Each step of the formation reaction of molybdosilicate from molybdic and silicic acids between pH 1 and 2 was clarified by ESI-MS at the molecular level. In a solution below pH 0.5, the polymers of the molybdic acids were decomposed because of the high concentration of sulfuric acid. Excess sulfuric acid prevented the formation of molybdosilicate. Thus, none of the silicic acids reacted to form molybdosilicate at this pH, despite the presence of silicic acid and sulfate ions in the solution. Above pH 2, the condensation of molybdic acids occurred to form α-molybdosilicate. ESI-MS provides information on the formation of molybdosilicate and the individual reaction species present in the reaction mixture.

Development and evaluation of an overseas clinical rotation program for undergraduate pharmacy students in Japan

BACKGROUND AND PURPOSEnInternationalization of pharmacists, as well as pharmacy students, in terms of both the knowledge to care for international patients and to have medical information literacy, is a current concern in Japan.nnnEDUCATIONAL ACTIVITY AND SETTINGnKeio University Faculty of Pharmacy has developed an elective course for pharmacy students, based on written agreements with the United States and Thailand that establish a student clinical rotation exchange program. The exchange program lasts for four to six weeks and involves clinical rotations in hospitals abroad during the students sixth year. Rotations follow a four-week didactic preparatory course. The course objectives are to acquire the knowledge, skills, and attitude needed to function as leading pharmacists with an international perspective.nnnMETHODSnWe asked students to complete a feedback survey inquiring about the usefulness of preparatory courses, self-evaluation pre- and post-rotation satisfaction with the program, and overall self-assessment.nnnFINDINGSnTwenty-fourxa0out ofxa041, i.e., 58.5% of the students replied with feedback. All respondents replied that the preparatory course was useful. They also replied that, based on their self-evaluation, they were satisfied with their level of English language skill improvement after the rotation. Pharmaceutical knowledge satisfaction, however, was slightly decreased. All respondents replied that this program was of a satisfactory nature, with 71%, 63%, and 92% of the respondents replying that they could acquire the knowledge, skills, and attitude program objectives respectively.nnnSUMMARYnIt is possible to successfully develop an overseas clinical rotation program. Students were quite satisfied upon completion and achieved the expected objectives.

Interprofessional education at the Keio University Faculty of Pharmacy

As part of a trial course on interprofessional education (IPE) at Keio University our Faculty of Pharmacy initiated a joint seminar with the university’s medical and nursing departments in 2008. We had two joint seminars: one in June and another in October. In the seminars, students and participants actively discussed several issues with regard to the national and private health care systems and medical malpractice. They also listened to feedback lectures held by experts from the medical and social system. At Kyoritsu University of Pharmacy, we had already held similar joint seminars three times since 2006. The participants were not only from our school but from various universities around Japan, given that our school was then only a small college for pharmaceutical students. Our considerable experience in the field of small group learning (SGL) helped make these seminars a success. By making full use of the SGL method we have successfully lead the discussion sessions at the IPE seminars attended by students from various medical fields. After the merging of our small pharmaceutical college with Keio University, we continued holding joint seminars for the three medical faculties at Keio University. It has not been without tribulations, however. The newly created interprofessional seminars faced several problems. The seeming lack of interest shown by the medical school decreased the level of participation of medical students, while too many facilitators are required for such seminars. To resolve these issues, we have made some changes to future activities in this area. To start with, we plan to change the course from an elective to a required subject for the students of the three medical faculties in Keio University.

Continuous separation of glucosides in dual-flow extraction system

A new separation system in dual-flow countercurrent extraction has been established. As a result, a two-component mixture could be separated with the improved apparatus, liquid particle extractor, whose working principle is the same as that in liquid particle chromatography (LPC). Liquid particle chromatography has been used as a means to determine the distribution constants of components in a sample, which were necessary for setting the operating condition of the extractor. The optimum condition for the best separation of two compounds (distribution constant of D1 and D2) was deduced theoretically. Thus, the flow rate of the aqueous phase (H) could be determined by a calculation using the flow rates of the sample feed (A, fed as an organic solution) and the organic phase (S) by the relation; H=(S+A/2)√ . With the extractor, a continuous and complete separation of phenyl-β-D-glucopyranoside (D=1.17) and esculin (D=1.58) in a 100mg-scale (100mg each in 20ml of water saturated 1-butanol) could be executed in 14h. A precise separation of a mixture with a separation factor (D1/D2) of 1.23 was also accomplished.