沙丁胺醇和特布他林与乳糖的美拉德反应产物的合成与表征以及在存在这些杂质情况下测定沙丁胺醇和特布他林的液相色谱法的开发与验证

Synthesis and Characterization of Maillard Reaction Products of Salbutamol and Terbutaline with Lactose and Development and Validation of an LC Method for the Determination of Salbutamol and Terbutaline in the Presence of These Impurities.

作者信息

El-Zaher Asmaa A, Fouad Marwa A, Elkady Ehab F

机构信息

Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

出版信息

Anal Chem Insights. 2014 Mar 2;9:1-7. doi: 10.4137/ACI.S13835. eCollection 2014.

Being secondary amines, both salbutamol (SLB) and terbutaline (TRB) react by Maillard reaction (MR) with lactose, which is added as an inactive ingredient in tablets. The Amadori rearrangement products were synthesized, isolated, and characterized by mass spectrometry. In addition, a simple, selective, and precise reversed-phase liquid chromatography (LC) method was developed and validated for the determination of SLB and TRB in tablets, each in the presence of its MR impurity. The chromatographic separation was performed on a Symmetry(®) Waters C18 column (150 mm × 4.6 mm, 5 μm) using a mobile phase consisting of 0.5% aqueous phosphoric acid to acetonitrile (90:10, v/v) at a flow rate of 0.7 mL minute(-1). Quantitation was achieved using UV detection at 230 nm. Linearity, accuracy, and precision were found to be acceptable for the determination of SLB and TRB in the concentration range of 0.2-60 and 0.5-80 μg mL(-1), respectively. The proposed method was successfully applied to the determination of SLB and TRB in bulk and in their tablets.

作为仲胺，沙丁胺醇（SLB）和特布他林（TRB）均通过美拉德反应（MR）与乳糖发生反应，乳糖作为片剂中的惰性成分添加。合成、分离了阿马多里重排产物，并通过质谱对其进行了表征。此外，开发并验证了一种简单、选择性好且精确的反相液相色谱（LC）方法，用于测定片剂中的SLB和TRB，且各自存在其美拉德反应杂质的情况下。色谱分离在Symmetry(®) Waters C18柱（150 mm × 4.6 mm，5 μm）上进行，流动相由0.5%的磷酸水溶液与乙腈（90:10，v/v）组成，流速为0.7 mL·分钟⁻¹。使用230 nm处的紫外检测进行定量。发现线性、准确度和精密度对于分别在0.2 - 60和0.5 - 80 μg·mL⁻¹浓度范围内测定SLB和TRB是可接受的。所提出的方法成功应用于原料药及其片剂中SLB和TRB的测定。