Kimie Imai

Hydroxyl Radical Scavenging Activity of Nonsteroidal Anti-Inflammatory Drugs

The hydroxyl radical (.OH)-scavenging activity of d-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid (M-5011), a novel nonsteroidal anti-inflammatory drug (NSAID), and that of several other NSAIDs were investigated by the hyaluronic acid (HA) degradation method and the electron spin resonance (ESR) spin-trapping technique. The superoxide anion (.O2-)-scavenging activity of M-5011 was also measured by the ESR technique. (1) M-5011 and the other NSAIDs examined inhibited the degradation of HA induced by the Fenton reaction system in a dose-dependent manner. (2) M-5011 and the other NSAIDs scavenged .OH directly in a dose-dependent manner. (3) M-5011 was the most potent drug among the NSAIDs tested regarding the scavenging activity of .OH as follows; M-5011 > indomethacin > ketoprofen = suprofen > aspirin. The .OH-scavenging activity of M-5011 was potent in comparison with that of oxidized glutathione (GSSG), an endogenous .OH scavenger. (4) M-5011 did not scavenge .O2-; nor did GSSG. These results suggest that M-5011 acts as a scavenger of .OH at sites with inflammatory lesions.

Validated method using liquid chromatography-electrospray ionization tandem mass spectrometry for the determination of contamination of the exterior surface of vials containing platinum anticancer drugs.

Contamination of the exterior surface of vials of cytostatic drugs by the drugs themselves is a potential hazard to human health. This study developed a validated method using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) for the determination of contamination of the exteriors of vials of cisplatin and carboplatin. Large Alpha® sampling swabs were employed to wipe the vial exterior. Cisplatin or carboplatin and gold(III) as an internal standard were derivatized by N,N-diethyldithiocarbamate (DDTC). Pt(DDTC)(3)(+) and Au(DDTC)(2)(+) were monitored by the respective transitions of m/z 639.3-490.9 and 493.0-345.0, respectively. Each separation was completed within 9 min using a 3 μm particle ODS-column. Calibration curves for cisplatin and carboplatin were linear over concentration ranges of 30-10,000 and 30-30,000pgvial(-1), respectively. The accuracies and precisions were 96.1-102.5% and within 8.2% for intra-assay and 99.6-103.3% and within 7.6% for inter-assay, respectively. Their lower limit of quantification was 30 pg vial(-1). Amounts of 0.17-17.0 ng vial(-1) as cisplatin and 0.48-794 ng vial(-1) as carboplatin were detected from the exterior surface of the vials. This validated method using LC-ESI-MS/MS for the determination of platinum anticancer drugs is helpful for monitoring contamination of the exterior surface of drug vials.

Effect of dietary fibers on losartan uptake and transport in Caco-2 cells.

The objective of this study was to assess the effect of dietary fibers on the transport of losartan, an angiotensin II type 1 receptor blocker, in small intestinal cells. Using Caco‐2 cells in vitro, losartan uptake and transport were evaluated in the presence of various fibers (cellulose, chitosan, sodium alginate and glucomannan). Dietary fibers caused a decrease in the uptake of losartan, with chitosan causing a significant reduction. Chitosan and glucomannan significantly reduced the transport of losartan, while cellulose or sodium alginate did not. Dietary fibers also reduced the level of free losartan; however, this did not correlate with the observed reduction in losartan uptake and transport. In summary, chitosan had the greatest inhibitory effect on losartan uptake and transport, and this potential interaction should be considered in patients taking losartan. Copyright