Contrasting Dynamics in Isoelectronic Anions Formed by Electron Attachment.

Cyanogen NCCN and cyanoacetylene HCCCN are isoelectronic molecules, and as such, they have many similar properties. We focus on the bond cleavage in these induced by the dissociative electron attachment. In both molecules, resonant electron attachment produces CN- with very similar energy dependence. We investigate the very different dissociation dynamics, in each of the two molecules, revealed by velocity map imaging of this common fragment. Different dynamics are manifested both in the excess energy partitioning and in the angular distributions of fragments. Based on the comparison with electron energy loss spectra, which provide information about possible parent states of the resonances (both optically allowed and forbidden excited states of the neutral target), we ascribe the observed effect to the distortion of the nuclear frame during the formation of core-excited resonance in cyanoacetylene. The proposed mechanism also explains a puzzling difference in the magnitude of the CN- cross section in the two molecules which has been so far unexplained.

Assay of terpene alcohols in pharmacopoeial essential oils by micellar electrokinetic capillary chromatography (MEKC).

Micellar electrokinetic capillary chromatography (MEKC) was used to separate and determine terpene alcohols of wide occurrence in herbal extracts and essential oils, namely eugenol, linalool, geraniol, citronellol and thymol. In the present paper sodium dodecyl sulfate (SDS) has been used as a micelle-forming additive to the CZE background electrolytes. Effects of SDS concentration, buffer type, its pH and concentration, addition of organic solvents on the migration times and separation efficiency were investigated. The optimal electrolyte system consisted of 20 mM TAPSO and 30 mM SDS in aqueous 10% (v/v) acetonitrile of pH 7.5 (adjusted by the addition of TRIS). The separation capillary was a fused silica tube (50 microm I. D., total length 75 cm, 42 cm effective length) maintained at 25 degrees C. The separations were performed at the applied voltage of 20 kV. Samples were injected hydrodynamically at a pressure of 50 mbar for 6 s. Detection was carried out at 200 nm. The calibration curves were rectilinear for 50-200 mg l(-1) (for eugenol, thymol and geraniol) and 100-400 mg l(-1) (for linalool and citronellol). The limits of detection varied between 5 mg l(-1) (for thymol) and 16 mg l(-1) (for linalool). The devised MEKC method was employed for the determination of the cited terpene alcohols as major quality-affecting constituents in commercial pharmacopoeial essential oils such as Geranii etheroleum, Caryophylli floris etheroleum, Lavandulae etheroleum and Thymi etheroleum. The results agreed well with those of a reference gas chromatographic method.

The identification of a chlorinated MDMA.

The abuse of the designer amphetamines such as 3,4-methylenedioxymethamphetamine (MDMA) is increasing throughout the world. They have become popular drugs at all night techno dance parties, and their detection is an important issue. The objective of the presented study was to identify an unknown compound detected by thin-layer chromatography (TLC) in the urine of an illicit drug abuser. The compound was isolated by TLC and analyzed by gas chromatography-mass spectrometry (GC-MS) in electron ionization (EI) and positive ion chemical ionization (PICI) mode to elucidate its chemical structure. Based on EI-MS and PICI-MS mass spectral data, the unknown compound was indicated to be a structure similar to MDMA, substituted by a single chlorine atom-a chlorinated MDMA (Cl-MDMA). To confirm the Cl-MDMA structure, the unknown compound was silylated, trifluoroacetylated, acetylated, heptafluorobutyrylated, and analyzed by GC-MS. The position of the chlorine atom cannot be assigned exactly from the mass spectral data presented here; however, we believe that the unknown compound could be 6-Cl-MDMA.

Determination of bopindolol in pharmaceuticals by capillary isotachophoresis.

Capillary isotachophoresis (ITP) with conductimetric detection has been used for separating and determining bopindolol (I) in commercial mass-produced pharmaceutical preparations. The optimised operational electrolyte system consisted of 5 mM potassium picolinate and 5 mM picolinic acid (leading electrolyte, LE; pH 5.37) and 10 mM formic acid as the terminating electrolyte (TE). The driving and detection currents were 50 microA (for 350 s) and 10 microA, respectively. The single analysis took about 12 min. Under such conditions the effective mobility of I was determined as 16.73 10(-9)m(2) V(-1) s(-1) (with tetraethylammonium as the mobility standard). The calibration graph relating the ITP zone length to the concentration of I was rectilinear (r=0.99990) in the range 10-100 mg l(-1). The relative standard deviation (R.S.D.) was 0.90% (n=6) when determining 50 mg l(-1) of I in pure test solution. Sample pre-treatment of the tablets involved ice-cooled extraction of I with methanol. The method was suitable for determining I in Sandonorm tablets with R.S.D. value 1.45% (n=6). According to the validation procedure based on the standard addition method the recovery was 97.3%.

Determination of tramadol in various dosage forms by capillary isotachophoresis.

Cationic capillary isotachophoresis (ITP) with conductometric detection has been used for separating and determining milligram amounts of tramadol [2-dimethylaminomethyl-1-(3-methoxyphenyl)-cyclohexanol hydrochloride] (I) in seven commercial mass-produced pharmaceutical preparations. The optimised ITP electrolyte system consisted of 5 mM potassium picolinate + 5 mM picolinic acid (pH 5.25) as the leading electrolyte and 10 mM formic acid as the terminating electrolyte. The driving and detection currents were 50 microA (for 320 s) and 10 microA, respectively (a single analysis took 12-15 min). Under such conditions the effective mobility of I was determined as 24.26 x 10(-9) m2 V(-1) s(-1) (with tetraethylammonium ion as standard); thermodynamic pKa value of I was 9.44 +/- 0.03 (n = 8) as determined by UV spectrophotometry at 25 degrees C and I = 0.01 (NaCl). The calibration graph relating the ITP zone length to the concentration of I was rectilinear (r = 0.99997) in the range 15-180 mg l(-1) of I. The relative standard deviation (RSD) was 0.21% (n = 6) when determining 60 mg l(-1) of I in pure test solution. Sample pre-treatment of the dosage forms involved dilution or extraction of I with water (for suppositories the extraction was carried out in an ultrasonic bath at 40 degrees C for 10 min). The method was suitable for determining 50 or 100 mg ml(-1) of I in injections and drops, 50 mg of I in capsules, and 100 mg of I in suppositories with RSD values 0.4 to 1% (n = 6). According to the validation procedure based on the standard addition technique the recoveries were 97.2-100.1% of I.

Separation and determination of sorbitol and xylitol in multi-component pharmaceutical formulations by capillary isotachophoresis.

Pharmaceutically important polyhydric alcohols sorbitol (SO) and xylitol (XY) are efficiently separated and determined by analytical capillary isotachophoresis (ITP) with conductometric detection. The on-column complex-formation equilibria between the polyols and boric acid are utilized--the terminating borate ion acts as the complexing agent. The ITP operational system used consists of 10 mM HCl + 20 mM imidazole (LE, pH 7.0) and 20 mM boric acid (TE, pH 8.0). The effective mobilities of the borated SO and XY are 8.3 x 10(-9) m2 V-1 s-1 and 7.4 x 10(-9) m2 V-1 s-1, respectively. The ITP analysis is performed with the driving and detection currents of 50 microA (for 700 s) and 20 microA, respectively. The calibration graphs are rectilinear in the range 25-250 mg l-1 of SO and 50 to 500 mg l-1 of XY. The method is applied to the simultaneous assay of SO and XY in three mass-produced multi-component infusion solutions. Favourable values of the method validation parameters obtained confirm the suitability of the proposed ITP method for the quality control of pharmaceuticals.

Determination of ambroxol or bromhexine in pharmaceuticals by capillary isotachophoresis.

Expectorant drugs ambroxol (AX) and bromhexine (BX) were determined by capillary isotachophoresis (ITP) with conductimetric detection. The leading electrolyte (LE) was a buffer solution that contained 5 mM picolinic acid and 5 mM potassium picolinate (pH 5.2). The terminating electrolyte (TE) was 10 mM formic acid. The driving current was 80 microA (for approximately 200 s) or 50 microA (for approximately 350 s) and the detection current was 20 microA (a single analysis took about 8 min). The effective mobilities of AX and BX (evaluated with tetraethylammonium as the mobility standard) were 18.8 x 10(-9) m2 V(-1) s(-1) and 14.3 x 10(-9) m2 V(-1) s(-1) respectively. The calibration graphs relating the ITP zone length to the concentration of the analytes were rectilinear (r = 0.9993-0.9999) in the range 10 mg L(-1) (20 mg L(-1) for BX) to 200 mg l(-1) of the drug standard. The relative standard deviations (RSD) were 1.2 1.6% (n = 6) when determining 100 mg l(-1) of the analytes in pure test solutions. The method has been applied to the assay of AX or BX in seven commercial mass-produced pharmaceutical preparations. According to the validation procedure based on the standard addition technique the recoveries were 97.5-102.7% of the drug and the RSD values were 0.11-2.20% (n = 6).

Capillary isotachophoretic determination of flufenamic, mefenamic, niflumic and tolfenamic acid in pharmaceuticals.

Anionic capillary isotachophoresis (ITP) with conductimetric detection has been used for determining selected non-steroid anti-inflammatory and analgesic drugs of the phenamate group, namely tolfenamic (I), flufenamic (II), mefenamic (III) and niflumic (IV) acid. Initially the pKa values (proton lost) of I-IV were determined as 5.11, 4.91, 5.39 and 4.31, respectively, by the UV spectrophotometry in aqueous 50% (w/w) methanol. The optimised ITP electrolyte system consisted of 10 mM HCl + 20 mM imidazole (pH 7.1) as the leading electrolyte and 10 mM 5,5'-diethylbarbituric acid (pH 7.5) as the terminating electrolyte. The driving and detection currents were 100 microA (for 450 s) and 30 microA, respectively (a single analysis took about 20 min). Under such conditions the effective mobilities of I-IV varied between 23.6 and 24.6 m2 V(-1) s(-1) (evaluated with orotic acid as the mobility standard). The calibration graphs relating the ITP zone length to the concentration of the analytes were rectilinear (r = 0.9987-0.9999) in the range 10-100 mg l(-1) of the drug standard. The R.S.D.s were 0.96-1.55% (n = 6) when determining 50 mg l(-1) of the analytes in pure test solutions. The method has been applied to the assay of the phenamates in six commercial mass-produced pharmaceutical preparations (Mobilisin gel and ointment, Lysalgo capsules, Nifluril cream, Niflugel gel, and Clotam capsules). According to the validation procedure based on the standard addition technique the recoveries were 98.4-104.3% of the drug and the R.S.D. values were 1.25-3.32% (n = 6).

Determination of some non-steroid anti-inflammatory drugs by capillary isotachophoresis.

The isotachophoretic (ITP) behaviour and separation of the anti-inflammatory drugs kebuzone (KB), tribuzone (TB) and phenylbutazone (PB) was studied in the operational system of HCl/His (leading electrolyte, LE) and 4-nitrophenol (terminating electrolyte, TE). The effective mobilities were 19.4 x 10(-9) m2 V-1 s-1 for KB, 18.1 x 10(-9) m2 V-1 s-1 for TB and 18.9 x 10(-9) m2 V-1 s-1 for PB when using an optimised system with 10 mM HCl + 40 mM His (pH 6.63) as LE and 10 mM 4-nitrophenol as TE. The calibration graphs were rectilinear (r = 0.9982-0.9996) in the range 20 to 600 mumol 1-1 of KB, TB or PB. The ITP method was used for determining the content of KB, TB or PB in mass-produced pharmaceuticals as tablets, coated tablets, injections, and ointments. The results of the ITP determination were in good agreement with those of standard pharmacopoeial methods.

Potentiometric determination of acetylsalicylic acid by sequential injection analysis (SIA) using a tubular salicylate-selective electrode.

This paper deals with the development of an automated procedure for formulation assays and dissolution tests based on a sequential injection analysis (SIA) system involving an ion-selective electrode as sensing device. Construction of a tubular salicylate (Sal) selective electrode suitable for potentiometric determination of acetylsalicylic acid (Asa) in pharmaceutical formulations is described. The flow-through electrode is formed by a PVC membrane containing 29.2% (w/w) PVC, 5.8% (w/w) tetraoctylammonium salicylate (ionic sensor), 58.5% o-nitrophenyloctylether (plasticizer) and 6.5% (w/w) p-tert-octylphenol (stabilising additive which increases electrode selectivity). The calibration range is 0.05--10 mM Sal, the limit of detection (LOD) is 0.05 mM Sal, the slope is 56.0 mV per decade at 22 degrees C. The R.S.D. is 0.20% (15 readings) when determining 2.5 mM Sal in standard solution. The electrode is used for sensing Asa after its on-line chemical hydrolysis to Sal in a SIA system. The sampling rate is 6 h(-1) but for the dissolution tests the frequency is increased to 20 h(-1). The SIA set-up is employed for the assay of Asa in plain tablets, composed tablets and effervescent tablets and for performing dissolution tests of normal and sustained release tablets. Results obtained by this technique compare well with those required by the US Pharmacopoeia XXIV.

Blood types of twin cattle after embryo transfer to inseminated recipients.

The blood types, together with erythrocyte and plasma protein types were determined in 10 pairs of twins born after embryo transfer to the contralateral uterine horns of previously inseminated recipients. These estimations were carried out at the age of nine weeks. According to the haemolytic test, most of these pairs of twins had identical blood types, ie, no erythrocyte mosaic could be demonstrated and the blood type corresponded to that of the recipient's calf. In the cases where mosaicism could be demonstrated, the recipient calf's blood type predominated. The reason for this bias remains unclear although the suggestion that the recipient's calf had developed further and was thus able to influence the haematopoietic tissues of its co-twin is worth considering.

[Electromigration analysis methods in quality control of pharmacopoeial herbal drugs]. / Elektromigracní analytické metody v kontrole kvality lékopisných rostlinných drog.

The present review paper surveys published electromigration methods for the determination of active substances occurring in plant drugs officinal in CL 97. The review involves the electrophoretic methods (CZE) that were used for the separation of different natural compounds including flavonoids, phenolic glycosides, anthraglycosides, cardiac glycosides, alkaloids, organic acids, amino acids, polypeptides, and proteins. The advantages and drawbacks of CZE methods relative to corresponding HPLC techniques are also discussed.

[Amperometric detection in the determination of drugs by non-separating flow methods--flow injection analysis and sequential injection analysis]. / Vyuzití amperometrické detekce (AD) pri stanovení léciv neseparacními prutokovými metodami--prutoková injekcní analýza (FIA) a sekvencní injekcní analýza (SIA).

The present review dealing with the use of various electrochemical detection systems in flow methods of analysis of drugs (such as FIA and SIA techniques). The review covers the period of 1988 to 1998 and involves 78 references. The drugs determined are arranged according to the functional groups undergoing electrochemical transformation; for all the analytes data on the detection conditions, detection limits and ranges of quantitation are included. Advantages and drawbacks of amperometric detection of drugs in flow systems are discussed.

[Oxidative determination of rutin in tablets using flow injection analysis and chemiluminescence]. / Oxidacní stanovení rutinu v tabletách metodou prutokové injekcní analýzy s chemiluminiscencní detekcí.

A simple, rapid and fully automated flow injection method (FIA) with chemiluminescence detection after oxidation with KMnO4 in acid medium at room temperature has been developed for the determination of routine in pharmaceutical formulation. Hexamethaphosphate sodium was utilized as enhancer of chemiluminescence. The calibration curve was linear in the range 0.01-0.26 mmol.l-1 with detection limit 0.005 mmol.l-1, RSD 0.46% (n = 10) and a sample throughput of 75.h-1 using a 200 microliters sample volume. The method was used for the determination of routine in mass-produced dosage form: Rutin 250 tablets á 50 mg, (firm Nature's Bounty, USA). The FIA method was statistically compared with the official German Pharmacopoeia method and showed comparable accuracy, but with the advantages of simplicity, speed and amounts of reagents consumed.

Determination of procaine, benzocaine and tetracaine by sequential injection analysis with permanganate-induced chemiluminescence detection.

Local anaesthetics procaine hydrochloride (I), benzocaine (II), and tetracaine hydrochloride (III) were determined by the technique of sequential injection analysis (SIA) with chemiluminescence (CL) detection. The CL was emitted during the oxidation of the analytes by permanganate in aqueous sulphuric acid in the presence of various CL enhancers (4-hydroxybiphenyl, Rhodamine B, glycolaldehyde, glutaraldehyde and formic acid). The optimum enhancer or reagent concentrations, order and volumes of the injected zones were: 0.37 M formic acid (40, 23 or 28 mul for I-III, respectively), sample (40 mul), 2.3 M H(2)SO(4) (20, 16 or 18 mul for I-III, respectively), and 0.5 mM KMnO(4) (19, 13 or 15 mul for I-III, respectively). After a double (or single for III) reversal of the flow the mixed zone was pushed into the detector at a flow rate of 100 mul s(-1). The transient CL signal was recorded at >/=390 nm. The calibration graphs relating the intensity of the emission (peak heights) to the concentration of the analytes were curvilinear (a second order polynomial showed the best fit) and they were suitable for determining I-III in the ranges 0.5-50, 0.5-25 and 0.2-25 mug ml(-1), respectively. The limits of detection (3sigma) were 0.3 mug ml(-1) for I and II and 0.1 mug ml(-1) for III. The sample throughput was 120 h(-1). The relative standard deviations were

Determination of limiting ionic mobilities and dissociation constants of some local anaesthetics.

The limiting ionic mobilities and thermodynamic acid dissociation constants were calculated from isotachophoretic experiments for the local anaesthetics procaine, tetracaine, lidocaine, trimecaine, bupivacaine, cinchocaine, diperodone, diocaine, cocaine, psicaine-neu, tropacocaine, amylocaine, beta-eucaine and leucinocaine. The pH values at which the local anaesthetics with very similar limiting ionic mobilities can be isotachophoretically separated were determined from simulated mobility curves. The measuring apparatus employed a high-frequency contactless conductivity detector.