Tramadol is an opioid used in the treatment of moderate to moderately severe pain. Tramadol’s use during pregnancy is generally avoided and may cause some reversible withdrawal effects in neonates, and its use during lactation is not licensed by the manufacturer. A small clinical trial reported infants were exposed to <3% of a mother’s tramadol dose through breast milk with no evidence of harmful effects. Presented is a case study of breast milk, neonatal urine, and neonatal oral fluid for the analysis of tramadol and its metabolites, along with the validation of a method for the analysis of tramadol, O-desmethyltramadol, and N-desmethyltramadol in breast milk. Tramadol and its metabolites were extracted by solid-phase extraction after saponification of breast milk to remove lipids. Samples were analyzed by ultra-pressure liquid chromatography-tandem mass spectrometry. To the author’s knowledge, this is the first report of tramadol and its metabolites in neonatal oral fluid. The breast milk concentrations were 63, 22, and 76 ng/mL for the analysis of tramadol, O-desmethyltramadol, and N-desmethyltramadol, respectively, on day of life 12. On day of life 20, the breast milk concentrations were 1,254, 388, and 937 ng/mL for the analysis of tramadol, O-desmethyltramadol, and N-desmethyltramadol, respectively. Oral fluid concentrations were 1,011, 1,499, and 406 ng/mL for the analysis of tramadol, O-desmethyltramadol, and N-desmethyltramadol, respectively, on day of life 20. Oral fluid concentrations were similar to breast milk for tramadol, almost four times higher for O-desmethyltramadol, and less than half for N-desmethyltramadol. The absolute infant dose was calculated to be 10 μg/kg/day and 294 μg/kg/day for tramadol on day of life 12 and 20, respectively.

中文翻译：

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新生儿通过母亲的母乳接触曲马多

曲马多是一种阿片类药物，用于治疗中度至中度重度疼痛。通常避免在怀孕期间使用曲马多，并且可能会对新生儿造成一些可逆的戒断作用，并且其在哺乳期间的使用未经制造商许可。一项小型临床试验报告称，婴儿通过母乳暴露于小于母亲 3% 的曲马多剂量，没有任何有害影响的证据。介绍了用于分析曲马多及其代谢物的母乳、新生儿尿液和新生儿口腔液的案例研究，以及对母乳中曲马多、O-去甲基曲马多和 N-去甲基曲马多的分析方法的验证。将母乳皂化去除脂质后，通过固相萃取法提取曲马多及其代谢物。通过超压液相色谱-串联质谱法分析样品。据作者所知，这是曲马多及其代谢物在新生儿口腔液中的首次报道。在第 12 天，用于分析曲马多、O-去甲基曲马多和 N-去甲基曲马多的母乳浓度分别为 63、22 和 76 ng/mL。在第 20 天，母乳浓度为 1,254， 388 和 937 ng/mL 分别用于分析曲马多、O-去甲基曲马多和 N-去甲基曲马多。在第 20 天分析曲马多、O-去甲基曲马多和 N-去甲基曲马多时，口腔液浓度分别为 1,011、1,499 和 406 ng/mL。曲马多的口腔液浓度与母乳相似，几乎是母乳的四倍O-去甲基曲马多更高，N-去甲基曲马多不到一半。曲马多在出生后第 12 天和第 20 天计算的婴儿绝对剂量分别为 10 μg/kg/天和 294 μg/kg/天。