Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., ET-11562 Cairo, Egypt; Analytical Chemistry Department, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Cairo, Egypt.
Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., ET-11562 Cairo, Egypt.
J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Nov 15;1132:121803. doi: 10.1016/j.jchromb.2019.121803. Epub 2019 Sep 13.
A novel, high throughput and sensitive LC-MS/MS assay method was developed and fully validated for quantitative determination of pioglitazone, its hydroxyl metabolite and alogliptin in human plasma. A simple and rapid sample preparation procedure based on protein precipitation technique with acetonitrile was utilized. Chromatographic separation was achieved on C (50 × 4.6 mm, 5 μm) Kinetex® analytical column using methanol and 0.1% formic acid in a gradient elution mode at a flow rate of 0.7 mL/min with injection volume of 8 μL. Detection was performed on a triple quadrupole mass spectrometer accompanied with electrospray ionization (ESI) technique in positive mode, operating in multiple reaction monitoring, with the transitions of 357.2 → 119.1, 373.1 → 150.1, 340.3 → 116.1, 361.1 → 138.1 and 343.2 → 116.1 m/z for pioglitazone, its hydroxyl metabolite, alogliptin, pioglitazone-d4 (IS-1) and alogliptin-d3 (IS-2), in order. Analysis was achieved within 4 min over a linear concentration range of 10-3000 ng/mL, 5-2000 ng/mL and 3-300 ng/mL, for pioglitazone, hydroxyl pioglitazone and alogliptin, in order. The method was fully validated according to FDA guidelines. The developed method was used for estimation of the three studied analytes in human plasma and pharmacokinetic parameters were demonstrated after oral dose administration of Oseni® tablets to Egyptian healthy volunteers.
开发并充分验证了一种新型、高通量且灵敏的 LC-MS/MS 测定法，用于定量测定人血浆中的吡格列酮、其羟基代谢物和阿格列汀。采用基于乙腈沉淀技术的简单快速的样品制备程序。色谱分离在 C （50×4.6mm，5μm）Kinetex®分析柱上进行，采用甲醇和 0.1%甲酸的梯度洗脱模式，流速为 0.7mL/min，进样量为 8μL。检测采用三重四极杆质谱仪，采用电喷雾电离（ESI）技术，正模式下进行，多重反应监测，转换为 357.2→119.1、373.1→150.1、340.3→116.1、361.1→138.1 和 343.2→116.1 m/z，用于吡格列酮、其羟基代谢物、阿格列汀、吡格列酮-d4（IS-1）和阿格列汀-d3（IS-2）。分析在 4 分钟内完成，线性浓度范围分别为 10-3000ng/mL、5-2000ng/mL 和 3-300ng/mL，用于吡格列酮、羟基吡格列酮和阿格列汀。该方法根据 FDA 指南进行了全面验证。该方法用于测定 Oseni®片剂给药后埃及健康志愿者人血浆中三种研究分析物的浓度，并展示了药代动力学参数。
