Department of Pharmacy, Okayama University Hospital, Japan.
Biol Pharm Bull. 2012;35(2):256-9. doi: 10.1248/bpb.35.256.
This is the first study to detect 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MTMP) from an intravenous injection bag solution by GC-MS. In previous studies, several other photoinitiators were reported to be very cytotoxic. Therefore, we theorized that photoinitiators such as MTMP might also have adverse cellular effects. The purpose of this study was to quantitate the amounts of contaminants from plastic containers such as those used for peripheral parenteral nutrition and to determine the cytotoxicity of such extracts on human monocytes. The sample extraction procedure for GC-MS analysis involved a liquid-phase extraction. The solvent was evaporated under a stream of nitrogen at 50°C. The residue was dissolved in n-hexane and injected into a GC-MS. Normal human peripheral blood mononuclear cells (PBMC), isolated from the buffy coat by centrifugation, were suspended in RPMI 1640 medium supplemented with 10% (v/v) heat-inactivated fetal calf serum. In the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cells (1×10(4)) were treated with MTMP for 24 h or 48 h at 37°C. From the GC-MS analysis, 5.62 ± 1.03 μg/mL of MTMP was found in the BFLUID(®) Injection 500 mL solution. In the MTT assay, MTMP decreased cell viability in a dose-dependent manner for both the 24 h and 48 h incubation periods. Our findings suggest that photoinitiators could promote adverse effects in patients. Future studies will clarify the possible health risks of photoinitiator accumulation in human cells.
这是第一项通过 GC-MS 从静脉注射袋溶液中检测 2-甲基-4'-(甲基硫代)-2-吗啉丙基苯甲酮（MTMP）的研究。在以前的研究中，报道了几种其他光引发剂具有非常细胞毒性。因此，我们推测像 MTMP 这样的光引发剂也可能对细胞有不良影响。本研究的目的是定量检测来自塑料容器（如用于外周肠外营养的容器）的污染物含量，并确定此类提取物对人单核细胞的细胞毒性。GC-MS 分析的样品提取程序涉及液相提取。溶剂在 50°C 的氮气流下蒸发。残留物溶解在正己烷中并注入 GC-MS。正常人外周血单核细胞（PBMC）通过离心从白细胞层中分离出来，悬浮在补充有 10%（v/v）热灭活胎牛血清的 RPMI 1640 培养基中。在 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）测定中，细胞（1×10(4))在 37°C 下用 MTMP 处理 24 小时或 48 小时。通过 GC-MS 分析，在 BFLUID(®)注射 500 mL 溶液中发现 5.62±1.03μg/mL 的 MTMP。在 MTT 测定中，MTMP 以剂量依赖性方式降低细胞活力，在 24 小时和 48 小时孵育期间均如此。我们的研究结果表明，光引发剂可能会促进患者产生不良反应。未来的研究将阐明光引发剂在人类细胞中积累的潜在健康风险。
