Bioequivalence data for two pharmaceutical formulations (solid oral dosage forms) containing carvedilol is presented for both racemic and enantiomers of the active substance. This was achieved by on-line coupling of two liquid chromatographic separations followed by fluorescence detection. The first LC dimension was used for a fast separation of racemic carvedilol from propranolol (IS) and the endogenous matrix, by means of a reversed phase mechanism. The peak of racemic carvedilol was on-line transferred to the second enantioselective LC dimension, based on a reversed phase separation on cellulose tris(3,5-dimethyl-phenylcarbamate) stationary phase. Both stages were monitored over a single run by means of a fluorescence detector operated at an excitation wavelength of 285 nm and an emission wavelength of 355 nm. Automated shortcutting of the racemic carvedilol peak to the chiral column and simultaneous detection over the two LC dimensions have been obtained by using an experimental set-up based on two six-port rotative switching valves. Linearity was demonstrated on the interval 2–150 ng/mL for racemic carvedilol and on 1–75 ng/mL intervals for enantiomers. LLOQ fits between 0.7 and 1.4 ng/mL. Recoveries of the target compounds are 87±4 and 81±4% for the IS. Precision ranged from 0.6 to 2.5% and the mean accuracy obtained on quality control samples (measured as % bias) over the whole study falls between −0.8 and 6.3%.

The effluents from the municipal wastewater treatment plants (WWTPs) are a major source of release of pharmaceuticals into the aquatic environment. The occurrence and removal efficiency of 9 pharmaceutical compounds of several classes in the WWTP of Bucharest were investigated using 24 h flow proportional composite influent and effluent samples. The compounds monitored during 9 days period were 6 antibiotics (trimethoprim, norfloxacin, ciprofloxacin, azithromycin, sulphametoxazole, erythromycin), an antiinflammatory drug (acetaminophen), an anticonvulsant (carbamazepine) and a nervous stimulant (caffeine). The analytes were identified and quantified using solidphase extraction and triple quadrupole LCMS/MS. All of the monitored compounds, except norfloxacin and erythromycin, were detected in influent and effluent wastewater. Acetaminophen (up to 30.16 μgL1) and caffeine (up to 74.54 μgL1) were the most abundant pharmaceutical compounds in untreated wastewater. Different compounds were removed to different extent in the WWTP, ranging from 0% for trimethoprim and carbamazepine to 95% for acetaminophen. Of all the antibiotics, ciprofloxacin although detected in the highest concentrations in the influent, in the range 0.90 – 4.97 μgL1 was removed comparatively more efficiently. Ciprofloxacin could have adverse effects on microorganism involved in biological treatment process and the others antibiotics escape WWTP processing, contaminating the receiving water bodies

A sensitive method for determination of free captopril as monobromobimane derivative in plasma samples is discussed. The internal standard (IS) was 5-methoxy-1H-benzimidazole-2-thiol. Derivatization with monobromobimane immediately after blood collection and plasma preparation prevents oxidation of captopril to the corresponding disulfide compound and enhances the ionization yield. Consequently, derivatization enhances sample stability and detection sensitivity. Addition of the internal standard was made immediately after plasma preparation. The internal standard was also derivatized by monobromobimane, as it contains a thiol functional group. Preparation of plasma samples containing captopril and IS derivatives was based upon protein precipitation through addition of acetonitrile, in a volumetric ratio 1:2. The reversed-phase liquid chromatographic separation was achieved on a rapid resolution cartridge Zorbax SB-C18, monitored through positive electrospray ionization and tandem MS detection using the multiple-reaction monitoring mode. Transitions were 408–362 amu for the captopril derivative and 371–260 amu for the internal standard derivative. The kinetics of captopril oxidation to the corresponding disulfide compound in plasma matrix was also studied using the proposed method. A linear log–log calibration was obtained over the concentration interval 2.5–750 ng/mL. A low limit of quantitation in the 2.5 ng/mL range was obtained. The analytical method was fully validated and successfully applied in a three-way, three-period, single-dose (50 mg), block-randomized bioequivalence study for two pharmaceutical formulations (captopril LPH 25 and 50 mg) against the comparator Capoten 50 mg.

The ESI–MS and MS/MS behavior of functionalized calix[4]arenes (1–5) has been studied in both positive and negative-ion mode. Liquid chromatography coupled to ESI–MS has been successfully used for separation of the byproducts issuing from the functionalization pathways, through the application of a simple reversed phase mechanism. The ability of (1–5) to host methyl esters of amino acids, tyrosine, tryptophan, phenylalanine, cysteine, valine, serine, leucine, isoleucine, and threonine has been evaluated by means of MS identification of the host– guest resulting in protonated molecular ions. The direct infusion within the ESI source of the solutions containing the two partners (i.e., calixarene and amino acid derivative) could act as a fast screening means for the evaluation of hosting capability. Only positive ionization may offer information about the host–guest complexes being formed. The influence of the excess of a partner in the infused solution strongly alters ionization yields, making quantitative approaches meaningless. Attempts to chromatographically isolate the host–guest complexes failed, probably due to the fact that interactions of the partners with the mobile and stationary phases are higher than the inclusion interactions. Structures consisting of combined fragments of the host–guest partners resulting from the collisional induced dissociation have not been observed.