A severe peak tailing was observed for adenosine 5'-monophosphate in flow injection analysis with stainless steel tubing and water/methanol mixture (1:1, v/v) as carrier. The cause of the peak tailing was investigated by focusing on the chemical structure of the analytes, the material used for the analytical systems and the composition of the carrier. We clarified that the peak tailing was caused by the interaction between phosphate residues in the analytes and stainless steel. The severe peak tailing did not occur with stainless steel tubing when the phosphate compounds were analyzed with carrier containing phosphoric acid or phosphate buffer. The findings indicate that such ill peak profiles are usually not considerable in conventional HPLC separation because phosphoric acid or phosphate buffer is quite commonly used in eluents. In LC-MS, however, the use of phosphoric acid and phosphate buffer is usually avoided because of their non-volatility; therefore this interaction between stainless steel and phosphate compound becomes predominant and results in severe peak tailings. We also found an effective method for avoiding the interaction. When stainless parts, such as LC tubing and ESI spray capillary, were treated with phosphoric acid prior to analysis, the peak profiles of the phosphate compounds were dramatically improved, even when non-phosphate buffer is used as carrier.
CMS-Na was safely administered to healthy volunteers but resulted in transient increase of urinary N-acetyl-β-D-glucosaminidase (NAG) and protein. Based on this study, the highest recommended dose of CMS-Na had sufficient bacteriostatic effect.
In healthy Japanese subjects, no safety concerns were found following repeat dosing of FF and VI or single dosing of FF, VI and FF/VI. Systemic exposure to FF and VI increased in a dose-dependent manner. Serum cortisol level was suppressed by 97% after 7 days repeat administration of FF at a dose of 800 μg. Heart rate with a single dose of VI 50 μg was higher than that of placebo, though not to a clinically significant extent.
It is important to select an appropriate surrogate matrix for preparing calibration standards and quality control samples while quantitatively assaying for endogenous substances, because a blank matrix that does not contain the endogenous substance cannot be derived from the species from which the target study samples are collected. This is because the assay results might be affected, depending on the characteristics of the analyte in the surrogate matrix. Our discussion group that participated in the Japan Bioanalysis Forum discussed the recommended selection strategies, focusing on large and small molecules in ligand binding assays and LC–MS, respectively. We established an efficient selection strategy for a surrogate matrix, with simple compositions as the first candidates stated in this article.
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