To obtain fundamental information on the drug incorporation into hair, time-course changes in drug distribution along single-strand hair were observed after a single oral administration of zolpidem (ZP), one of the most frequently used hypnotic agents. Quantitative sectional hair analyses of 1-mm segments were performed for each single-strand hair using a validated LC-MS/MS procedure. ZP was detected in all specimens plucked at 10 and 24 hours after a single dose, and the distribution ranged over the whole hair root (4-5 mm in length). A significantly high concentration of ZP was detected in the hair bulb region, whereas much lower concentrations were widely observed in the upper part of the hair root of those samples; this suggested that the incorporation of ZP occurred in two regions, mainly in the hair bulb and to a lesser extent in the upper dermis zone. The ZP-positive area formed lengths of up to 10-12 mm after a single administration, indicating that its incorporation from the hair bulb would continue for about 2 weeks. Time-course changes in the ZP concentration in the hair root additionally revealed that only a small portion of ZP that initially concentrated in the bulb was successively incorporated into the hair matrix and moved toward the keratinized region as hair grew. These findings should be taken into account upon discussing individual drug-use history based on hair analysis. The matrix-assisted laser desorption/ionization mass spectrometry imaging of ZP in the same kinds of hair specimens was also successfully achieved.

No abstract

The four-electron oxygen reduction reaction (4e–-ORR) is the mainstay in chemical energy conversion. Elucidation of factors influencing the catalyst’s reaction rate and selectivity is important in the development of more active catalysts of 4e–-ORR. In this study, we investigated chemical and electrochemical 4e–-ORR catalyzed by Co2(μ-O2) complexes bridged by xanthene (1) and anthracene (3) and by a Co2(OH)2 complex bridged by anthraquinone (2). In the chemical ORR using Fe­(CpMe)2 as a reductant in acidic PhCN, we found that 1 showed the highest initial turnover frequency (TOFinit = 6.8 × 102 s–1) and selectivity for 4e–-ORR (96%) in three complexes. The detailed kinetic analyses have revealed that the rate-determining steps (RDSs) in the catalytic cycles of 1–3 have the O2 addition to [CoII 2(OH2)2]4+ as an intermediate in common. In the only case that complex 1 was used as a catalyst, k cat depended on proton concentration because the reaction rate of the O2 addition to [CoII 2(OH2)2]4+ was so fast as compared to that of the concerted PCET process of 1. Through X-ray, Raman, and electrochemical analyses and stoichiometric reactions, we found the face-to-face structure of 1 characterized by a slightly flexible xanthene was advantageous in capturing O2 and stabilizing the Co2(μ-O2) structure, thus increasing both the reaction rate and selectivity for 4e–-ORR.

In order to investigate the incorporation behavior of drugs into hair in early stage (within 24 h) after intake, time-course changes in drug distribution in black hair were carefully analyzed after a single oral administration of methoxyphenamine (MOP), a non-regulated analog of methamphetamine. Single-hair specimens collected by plucking with the roots intact at appropriate intervals post-intake were each divided into 1-mm segments from the proximal end, and MOP in each segment was determined by a validated liquid chromatography-tandem mass spectrometry procedure. At 10 min after intake, MOP was not detected in any of the segments. MOP became detectable 30 min after intake in the hair bulb (0–1-mm segment from the proximal end) and 1 h after intake in the upper dermis zone (1–2-mm to 4–5-mm segments). The amount of MOP in the hair bulb increased rapidly over 3 h after intake and reached a maximum concentration of about 100–900 pg/1-mm single hair (11–95 ng/mg) around 3–10 h after intake, whereas that in the upper dermis zone increased at a more gradual pace over 24 h and reached a plateau at about 30–100 pg/1-mm hair (3–11 ng/mg). These differences can be attributed to their different incorporation mechanisms. Results from this study can further elucidate the drug incorporation mechanism, which is crucial for accurately interpreting results in hair analyses. Our findings also suggest that hair drugs analysis with special attention to the hair root can serve as a useful complementary approach to urine- and blood-based testing in the field of forensic toxicology.

No abstract