Institute of Clinical Pharmacology, Medical Faculty, Technical University Dresden, Germany.
Institute of Clinical Pharmacology, Medical Faculty, Technical University Dresden, Germany.
J Chromatogr A. 2018 Jun 29;1556:73-80. doi: 10.1016/j.chroma.2018.04.068. Epub 2018 May 4.
A rapid and sensitive hydrophilic interaction liquid chromatography (HILIC)-tandem mass spectrometry method was developed and fully validated for the simultaneous determination of the antidiabetic drug metformin and six further pharmaceuticals (atenolol, gabapentin, levofloxacin, ciprofloxacin, propranolol and trimethoprim) in influent and effluent wastewater. Five deuterated related compounds were used as internal standards in order to control the extraction, injection and ionization variability. Two solid phase extraction methods and Oasis HLB 1cc cartridge, using only 1mL sample with acid or basic pH-value were optimized and compared in order to match the specificity of both influent and effluent wastewater matrixes. The most important challenge was to efficiently extract the polar compound metformin from the aqueous matrix. This was possible by adjusting the sample pH to 10. On the other hand, the adjustment to acid pH prevents metformin binding on the SPE cartridges. Metformin was so directly recovered after passing through the cartridge and injected in the HPLC-MS/MS system without any other preparation. These two methods present advantages and drawbacks, but are both applicable to wastewater samples. The method with extraction at pH 3 was applied to influent wastewater samples and metformin concentrations higher than 625ng/L. On the other hand, the extraction method at pH 10 with a lower limit of quantification for metformin of 156ng/L was successfully applied to effluent water and to surface water samples. Both methods were fully validated. Limits of quantification were sufficiently low to provide good analytical performances for the determination of all drugs in both influent and effluent wastewater. Wastewater samples collected from six different wastewater treatment plants in Germany were analyzed. All analytes were present in influent samples at concentrations above the lower limit of quantification LLOQ, particularly metformin which presents concentrations up to 300μg/L.
建立并充分验证了一种快速灵敏的亲水作用色谱（HILIC）-串联质谱法，用于同时测定进水和出水中的降糖药物二甲双胍和其他六种药物（阿替洛尔、加巴喷丁、左氧氟沙星、环丙沙星、普萘洛尔和甲氧苄啶）。使用 5 种氘代相关化合物作为内标，以控制提取、进样和离子化的可变性。优化并比较了两种固相萃取方法和 Oasis HLB 1cc 小柱，仅使用 pH 值为酸性或碱性的 1mL 样品，以匹配进水和出水基质的特异性。最重要的挑战是从水性基质中有效地提取极性化合物二甲双胍。通过将样品 pH 值调节至 10 可以实现这一点。另一方面，调节至酸性 pH 值可防止二甲双胍与 SPE 小柱结合。二甲双胍直接从小柱中通过并注入 HPLC-MS/MS 系统后无需任何其他制备即可直接回收。这两种方法各有优缺点，但都适用于废水样品。在 pH 3 下进行萃取的方法适用于进水废水样品，且二甲双胍浓度高于 625ng/L。另一方面，在 pH 10 下进行萃取的方法，二甲双胍的定量下限为 156ng/L，成功应用于出水和地表水样品。两种方法均经过充分验证。定量下限足够低，可在进水和出水中测定所有药物时提供良好的分析性能。分析了来自德国六个不同污水处理厂的废水样品。所有分析物均在进水样品中存在，浓度高于定量下限，特别是二甲双胍的浓度高达 300μg/L。
