A probe of new molecularly imprinted solid-phase extraction coupled with HPLC-DAD and atomic absorption spectrophotometry for quantification of tetracycline HCl, metronidazole and bismuth subcitrate in combination with their official impurities: Application in dosage form and human plasma

•Tetracycline HCl, metronidazole and bismuth subcitrate have been combined recently.•An analytical approach for simultaneous determination of these drugs in plasma.•A molecularly imprinted solid-phase extraction with HPLC was employed.•Atomic absorption spectrometry for bismuth subcitrate quantification.•Determination with two related official impurities. The integration of molecular imprinting technique with chromatographic one has a great impact on the assay’s selectivity and sensitivity. Herein, a molecularly imprinted solid-phase extraction associated with high performance liquid chromatography (MISPE-HPLC) was employed for simultaneous determination of the co-formulated drugs; tetracycline hydrochloride (TET) and metronidazole (MET), in plasma and in their anti-H-pylori drug for the first time. Two sorts of molecularly imprinted polymers (MIPs) were fabricated using TET and MET as the template molecules, while ethylene glycol dimethacrylate and methacrylic acid were used as a cross-linker and a monomer, respectively. The synthesized MIPs were identified using different techniques. The adsorption–desorption capability of each template was investigated towards its corresponding MIP. The extraction conditions of MISPE was optimized with respect to TET/MIP and MET/MIP sorbent. Bismuth subcitrate (BSC), the third co-formulated drug was analyzed in spiked human plasma using an atomic absorption spectrometric (AAS) method. The performance of the developed methods was assured as per ICH guidelines for analyzing the studied drugs in their pharmaceutical dosage form along with two of their official impurities. In addition, bioanalytical method validation was conducted where linearity was achieved at 2.0–40.0 μg mL−1, 2.0–40.0 μg mL−1 and 5.0–80.0 μg mL−1 for TET, MET and BSC, respectively.