Qternmet XR® (FDA approval, May 2019) is a multitarget anti-diabetic drug combination composed of metformin (MET), saxagliptin (SAX) and dapagliflozin (DAP). To our present knowledge, no analytical reports were found in the scientific databases for the simultaneous quantification of MET, SAX and DAP in their ternary combined tablets, moreover, no articles have attempted the simultaneous estimation of the cited drugs in any matrix using high-performance liquid chromatography with diode-array detection (HPLC–DAD) or high-performance thin-layer chromatography (HPTLC) technique. The current work represents a comparative study on two developed and validated chromatographic methods for the simultaneous determination of the ternary mixture (MET, SAX and DAP) in pure form and in combined tablet dosage form. The first method is reversed-phase HPLC using Agilent C18 column (4.6 × 250 mm, 5 μm p.s.) with a mobile phase consisting of acetonitrile and acidic aqueous phase pH 3 with a photodiode array detection at 230 nm. The second method is HPTLC in which drug solutions were applied to Merck HPTLC silica gel plates developed with a mixture of chloroform:methanol:water:acetic acid (7.4:2.6:0.5:0.01, v/v) and scanned at 224 nm. Both methods were fully validated following the ICH guidelines in terms of linearity, accuracy, precision, selectivity and robustness.

Representative HPLC (a) and HPTLC (b) chromatograms for a ternary mixture of metformin (MET), saxagliptin (SAX) and dapagliflozin (DAP)

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HPLC-DAD与HPTLC同时测定组合片剂中新的多靶点抗糖尿病三元混合物的比较研究

QternmetXR®（FDA批准，2019年5月）是一种多靶点抗糖尿病药物组合，由二甲双胍（MET），沙格列汀（SAX）和达格列净（DAP）组成。据我们目前所知，在科学数据库中未发现用于同时定量其三元组合片剂中的MET，SAX和DAP的分析报告，此外，还没有文章尝试使用高性能方法同时估算任何基质中的被引药物液相色谱，采用二极管阵列检测（HPLC-DAD）或高性能薄层色谱（HPTLC）技术。目前的工作是对两种同时测定纯形式和片剂组合形式三元混合物（MET，SAX和DAP）的色谱方法进行比较和验证的比较研究。第一种方法是使用Agilent C18色谱柱（4.6×250 mm，5μmps）进行反相HPLC，其流动相由乙腈和酸性水相pH 3组成，并在230 nm处检测光电二极管。第二种方法是HPTLC，其中将药物溶液应用到用氯仿：甲醇：水：乙酸（7.4：2.6：0.5：0.01，v / v）并在224 nm扫描。两种方法均按照ICH准则在线性，准确性，精密度，选择性和鲁棒性方面得到了充分验证。

二甲双胍（MET），沙格列汀（SAX）和达格列净（DAP）三元混合物的代表性HPLC（a）和HPTLC（b）色谱图