Raluca-Ioana Stefan

Ion-Selective Membrane Electrodes in Pharmaceutical Analysis

Abstract The improving of knowledge about the ion-selective electrodes membrane configuration and mechanism of potential development rendered the quality of analytical information obtained by ion-selective membrane electrodes utilization to increase. Some important ionselective membrane electrodes described for the pharmaceutical analyses are presented. Also, one of the most recently introduced important class of membrane electrodes, namely, the enantioselective-membrane electrodes class, is presented briefly.

ENANTIOSELECTIVE SENSORS AND BIOSENSORS IN THE ANALYSIS OF CHIRAL DRUGS

The opportunity to use electrochemical sensors in enantioselective analysis is discussed. Chiral selectors such as crown ethers, cyclodextrins, and enzymes had been used for both chromatographic enantioseparation methods and enantioselective electrochemical sensors and biosensors. New possibilities of membranes construction, like molecular imprinting-based enantioselectivity sensors are also discussed. The advantages of use enantioselective sensors and biosensors over separation methods (HPLC, MEKC, CZE) are presented. The reliability of chiral drugs enantioselective assay is improved by using enantioselective sensors and biosensors.

Quality and Reliability in Analytical Chemistry

Quality in Chemical Analysis The Reliability in the Analytical Chemistry The Reliability of the Sampling The Connection between Reliability and Analytical Method The Connection between Reliability and Instruments The Reliability of Data Processing Analytical Process The Role of Standards and Standardization on Reliability of the Analytical Information References

Amiodarone-selective membrane electrode

Abstract A liquid membrane electrode based on an amiodarone-dipicrylamine ion-pair complex, dissolved in nitrobenzene as solvent, is proposed for the determination of amiodarone, an antiarrhythmic drug. The linear response covers the range 10−2–10−5 M amiodarone solution, with a slope of 57.3 mV/decade (pH range 0.80 to 4.80). The detection limit is 4 × 10−9 M. The electrode shows a good stability, reproducibility and fast response. The selectivity is good against K+ and Ca2+. There are two strong interfering ions, ephedrine and polyvinylprolidone. The characteristics of the electrode make it useful for the determination of amiodarone by direct and indirect potentiometric methods. Through the indirect potentiometric method, amiodarone can be determined as an active substance with an average recovery of 99.60% and a relative standard deviation of 0.67%, and this method can also be used for its determination in pharmaceutical dosage forms such as tablets and ampoules with a relative standard deviation less than 1%. The electrode can also be used for dissolution tests of amiodarone tablets. The physical processes are numerically simulated by typical equations. The apparent first-order rate constants for disintegration and dissolution processes have been calculated.

Validation criteria for developing ion-selective membrane electrodes for analysis of pharmaceuticals

The problem of validation criteria for developing ion-selective membrane electrodes for the analysis of pharmaceuticals arises from the connection between the reliability of ion-selective membrane electrodes construction and the reliability of the analytical information. Liquid membrane selective electrodes are more suitable for validation than the solid variety. The influence of the stability of ion pair complexes from the membrane on various parameters (e.g. response, limit of detection, and selectivity) is discussed. Validation criteria are proposed.

Ion-Selective Membrane Electrodes: Membrane Configuration

Abstract A membrane configuration is proposed, based on ion and electron transfers. The membrane equilibria are analyzed. From this point of view, a theoretical function model is discussed.

Moclobemide-selective membrane electrode and its pharmaceutical applications

A liquid membrane electrode prepared with moclobemide-dipicrylamine ion-pair complex, dissolved in nitrobenzene as solvent, was studied for analytical performance. The linear response covers the range 10(-3)-10(-6) M moclobemide solution, with a slope of 50.7 mV decade(-1) (pH range 3.5-8). The detection limit is 3 x 10(-7) M. The electrode shows stability, good reproducibility and fast response. The selectivity of the electrode is good. There are two important interfering ions: mianserin and thiamine (Vitamin B(1)). The compression excipients (such as Mg(2+), starch, talcum powder) do not interfere. These characteristics of the electrode enabled it to be used for the determination of moclobemide in drugs and as an active substance, via indirect and direct potentiometric methods. Via an indirect potentiometric method moclobemide, as an active substance, can be determined with an average recovery of 99.96% and a relative standard deviation of 0.85%, and this method can also be used for its determination in drugs with a relative standard deviation of < 2%. The electrode is useful for the determination of the dissolution rate of moclobemide tablets. The physical processes are numerically simulated by typical equations. The apparent first-order rate constants for disintegration and dissolution were calculated.

Biosensors for the enantioselective analysis of S-enalapril and S-ramipril.

S-Enalapril, and S-ramipril are angiotensin-converting enzyme (ACE) inhibitors which are used for treatment of hypertension. Due to the fact that only the S enantiomer possesses the ACE inhibiting activity, it is necessary to develop an enantioselective analytical method for its discrimination from the less active R-enantiomer. An amperometric biosensor, based on L-amino acid oxidase, was developed and proved reliable for the analysis of the S-enantiomer of these ACE inhibitors. The working range of the biosensor for S-enalapril assay (A) is 0.4-120 mumol/L, and for S-ramipril assay (B) is 0.2-100 mumol/L, with a limit of detection of 163 nmol/L (A) and 107 nmol/L (B), respectively. It is of interest to mention that the biosensors demonstrated enantioselectivity versus D-proline (1.4 x 10(-3) mol/L(A), 5.3 x 10(-3) mol/L(B) and also the selectivity versus the polyvinylpyrolidone (3.0 x 10(-3) mol/L(A), 3.2 x 10(-3) mol/L(B), respectively. The working pH ranges are: 6.8-7.4 (A), and 6.2-7.0 (B), respectively. The RSD < 1% assured by using the amperometric biosensors for S enantiomers assay in raw materials, in tablet formulations, and their suitability for the analysis of these drug enantiomers.

Biosensor for enantioselective analysis of S-cilazapril, S-trandolapril, and S-pentopril

The purpose of this research was to construct an amperometric biosensor on L-amino acid oxidase (L-AAOD) supported on a carbon paste for the enantioselective analysis of S-cilazapril (I), S-trandolapril (II), and S-pentopril (III). A chemically modified carbon paste was constructed with L-AAOD. The proposed amperometric biosensor proved reliable for the purity of I, II, and III. The linear working ranges obtained for drug assay were 0.001-100 mumol/l (I), 0.02-10 mumol/l (II), 0.08-50 mumol/l (III) over the pH ranges 7.0-7.4 (I), 6.8-7.4 (II), and 7.0-7.4 (III). The low limits of detection obtained were 5 pmol/l (I), 15 mumol/l (II), and 5 mumol/l (III), respectively. The selectivity of the biosensors was checked by both mixed and separate solution methods. Polyvinylpyrolidone and D-proline did not interfere with the assay of the studied drugs, whereas L-proline presented a potent interfering species. The relative standard deviation values (< 0.2%) make the biosensors suitable for direct amperometric assay of these angiotensin-converting enzyme (ACE) inhibitors. The proposed amperometric biosensor that was based on L-AAOD proved reliable in the analysis of the above-mentioned ACE inhibitors and can be used for the quality control of these drugs.

Solvent Extraction of Amino Acids With Crown Ethers and Cryptand 222

Abstract The possibility of crown ethers: 18 - crown - 6 (18C6), benzo - 18 - crown - 6 (B18C6), dibenzo - 18 - crown - 6 (DB18C6) and cryptand 222 (222) to form complexes with the cationic species of a series of α - amino acids in the protonated form (L - leucine, L - isoleucine, L - phenylalanine, L - methionine, L - valine and L - α-alanine) has been investigated. These cationic complexes can be extracted in chloroform, as ion pair complexes using pirate anion as counterion. The extraction constants have been determined by UV - Vis absorption method and they are in the 4.2 - 5.28, 4.19 - 4.54, 3.5 - 4.25, and 4.15 - 4.49 ranges when 18C6, B18C6, DB18C6 crown ethers, and 222 cryptand, respectively are used.