Cyclodextrin-based potentiometric sensors for midazolam and diazepam

In this work the implementation of benzodiazepine ion-selective electrodes for pharmaceutical formulations control is described. The solid-contact electrodes for midazolam and diazepam are based on polymeric membranes incorporating respectively β-cyclodextrin and (2-hydroxiproyl)-γ-cyclodextrin as ionophores, 2-fluorophenyl 2-nitrophenyl ether as plasticizer and potassium tetrakis (p-chlorophenyl) borate as ionic additive. For conventionally shaped midazolam electrode a slope of 61.9 ± 1.3 mV dec−1, a LLLR of 5.7 ± 2.7 × 10−4 g L−1 and pH range of 2.6–5.4 was obtained, while the corresponding values for diazepam electrodes were of 67.6 ± 3.0 mV dec−1, 4.9 ± 1.5 × 10−2 g L−1 and 1.9–2.7 pH units, respectively. Membrane optimization was based on the molar ratio between the ionophore and additive for midazolam and on inclusion cavity of cyclodextrin for diazepam. The miniaturization of the above-described electrodes gave rise to potentiometric detectors for sequential-injection lab-on-valve system with similar characteristics albeit the useful lifetime shortened from 1 year to approximately 15 days under continuous operation. The optimized flow conditions were achieved for sample injection volumes of 20 μL propelled towards the detection cell at the flow rate of 16 μL s−1 during 80 s. Real sample analysis revealed statistical accuracy and between-days precision comparable to the general used chromatographic-based procedure.