Therapeutic drug monitoring of tacrine: simple and fast high-performance liquid chromatography assay method for its determination in human plasma.

A new high-performance liquid chromatography (HPLC) assay method was developed for the therapeutic monitoring of tacrine. The method involved a simple protein precipitation by means of either acetonitrile or cold methanol followed by a fast isocratic separation on a CN column eluted in reversed-phase mode. The entire sample preparation took place in an HPLC vial and no further liquid transfer was required. The validation data showed that the assay method was precise, accurate, and robust. Analysis of more than 1,000 plasma samples collected from patients with Alzheimer disease demonstrates the suitability of the assay.

Gas chromatography-mass spectrometry assay method for the therapeutic drug monitoring of the antiepileptic drug tiagabine.

A gas chromatography-mass spectrometry assay method suitable for the therapeutic drug monitoring of the antiepileptic drug tiagabine is described. Tiagabine and its desmethylated analogue used as internal standard were first extracted from serum by liquid-liquid extraction using an ethyl ether-isobutanol 98:2 mixture. Tiagabine and the internal standard were then methylated in the organic phase in presence of methanol by means of a safe and stable diazomethane derivative. After evaporation, the reconstituted extracts were chromatographed on a crosslinked phenyl methyl siloxane capillary column and detected by mass fragmentometry at m/z = 156. No other antiepileptic drug possibly administrated in polytherapy and no metabolite were found to interfere in the assay. The limit of quantification was 5 ng/ml. The precision and the accuracy were found to be suitable for the therapeutic drug monitoring of tiagabine.

Determination of dimethindene in human tears by high-performance liquid chromatography.

A high-performance liquid chromatographic method is described for the determination of dimethindene in human tears. The tear samples were diluted in a 0.01 M hydrochloric acid-n-propanol mixture to prevent the irreversible adsorption of dimethindene. The diluted samples were directly injected into the chromatographic system to avoid sample pretreatment. The validation data demonstrate that the method is specific, precise and accurate within the calibration range of 12 to 1000 ng/ml dimethindene free base.

Extrapolation of molar equilibrium constants to zero ionic strength and parameters dependent on it. Copper(II), nickel(II), hydrogen(I) complexes with glycinate ion and calcium(II), hydrogen(I) complexes with nitrilotriacetate ion.

The stability constants of the complexes of glycinate ion with copper(II), nickel(II) and hydrogen(I) and of nitrilotriacetate ion with calcium(II) and hydrogen(I) and the ionic product of water (K(w)) were determined potentiometrically. The measurements were carried out at 25.0 degrees C in four different ionic strengths up to I (= I(c)) = 2.50 and two different ionic media (KNO(3) and (CH(3))(4)NNO(3)). Extrapolation of equilibrium constants to zero ionic strength and ionic strength corrections to equilibrium constants were carried out with the data obtained from both media using the TEC (thermodynamic equilibrium constant) equation and computer program. The constants of the potassium complexes with nitrilotriacetic acid at low ionic strength are also given. Successful attempts to predict equilibrium constants for other ionic media using TEC parameters and the procedure of the specific ion-interaction theory (SIT) are given. The variations of equilibrium constants with the ionic strengths and ionic media are demonstrated.

The extrapolation of experimental equilibrium constant data to zero ionic strength: Critical review and new approach.

Different Debye-Hückel expressions for the activity coefficients of species in aqueous solution in the ionic strength range I = 0-3.5m (3M) are used for the extrapolation of equilibrium constants data to I = 0 and the interpolation to unknown I values. This may be accomplished using four or more values of the equilibrium constants that are equally well distributed on the I scale. The interpolated and extrapolated equilibrium constant values obtained are quite satisfactory and within the experimental error of the corresponding equilibrium constants. The values at I 0.1 are very important as they can particularly influence the equilibrium constant value calculated at I = 0 and for which the error can reach 0.1 log unit or more. The values at I 1.5 can also influence the extrapolated value at I = 0 and the interpolated value at a given I when an inadequate extrapolation model is selected. Among the expressions used, only those with two or more unknown parameters are suitable for such calculations.

The investigation of complex formation equilibria at constant ionic strength.

The inert salts used for the investigations of complex formation are briefly discussed in relation to the effects of their ions on the equilibria studied. In general, some association with the inert salt ions cannot be completely avoided. In case of very stable complexes measured at low ionic strength, their effects can be quantified even though they are not caused by the anion if NO(-)(3) or ClO(-)(4) are used. In the case of weak complexes, when ionic strengths I > or =1 are used, the concentration of the complex of interest can be 1000 times lower than that of the associates of the same cation with the anion of the inert salt causing difficulties with the investigation of the latter systems. If the experimental results for K(1) of the alkaline-earth metal ions with fluoride in sodium perchlorate and sodium nitrate are correct, as their equilibrium constants have very similar values, it follows that the behavior of two anions is very similar. However, if NO(-)(3) associates with the above cations, as found, the same behavior is expected for ClO(-)(4). A more accurate analysis can only be done if activity coefficients in these solutions are known.

Chemical and biological properties of a cationic Tc-tetraamine complex.

The complex of 99Tc with the ligand 1,4,8,11-tetraazaundecane (2,3,2-tet) was prepared and was compared with the similar 99Tc complexes with ethylenediamine and 1,4,8,11-tetraazacyclotetradecane. The results are all consistent with the formula [TcO2(2,3,2-tet)]+. The biological behavior was tested with 99mTc in Wistar rats. A fast clearance via the kidneys was found, and no accumulation in any other organ was observed.