Improved compatibility of liquid chromatography with electrospray tandem mass spectrometry for tracing occurrence of barbital homologous residues in animal tissues.

This work describes a liquid chromatography-tandem mass spectrometry (LC-MS/MS) procedure for multiplex screening, ultratrace quantification and reliable confirmation of barbital series residues in animal-derived food matrices. The method is developed based on a distinct dependency of the electrospray ionization (ESI) response of nine structural homologues on LC eluent properties and gas-phase ion chemistry during the ESI process. The "wrong-way-round" negative ionization aspect has been explored to optimize the compatibility of the hyphenated LC-MS/MS technique, which facilitates detection limits at 30-100-fold lower than 0.01 ppm without derivatization or post-column basification step. A mobile phase using methanol modified with 0.01% acetic acid is adopted to achieve an approximately 2-9-fold increase in signal-to-noise ratio over the results under suboptimal conditions. There is no significant differential matrix effects or deuterium isotope effects on chromatographic retention and ESI responsiveness at all levels across the different analyte-matrix pairs. Mean recoveries ranged from 79.6% (barbital) to 108% (secobarbital) at fortified levels of 0.5-20 ng/g within relative standard deviations less than 11%. Between-run repeatability and within-laboratory reproducibility were 3-11% and 5-13%, respectively. An ion ratio criterion for valid detection limit data for simultaneous screening of homologous multiresidues in complex sample matrices is proposed. The satisfactory applicability of the newly described procedure to 43 real samples including pork, poultry meat, swine liver, fish tissue and shrimp muscle demonstrated the LC-MS/MS technique with facile sample handling can serve as an attractive alternative analytical method accepted for regulatory purpose.

Multiwalled carbon nanotubes as a solid-phase extraction adsorbent for the determination of three barbiturates in pork by ion trap gas chromatography-tandem mass spectrometry (GC/MS/MS) following microwave assisted derivatization.

A new method was developed for the rapid screening and confirmation analysis of barbital, amobarbital and phenobarbital residues in pork by gas chromatography-tandem mass spectrometry (GC/MS/MS) with ion trap MSD. The residual barbiturates in pork were extracted by ultrasonic extraction, cleaned up on a multiwalled carbon nanotubes (MWCNTs) packed solid phase extraction (SPE) cartridge and applied acetone-ethyl acetate (3:7, v/v) mixture as eluting solvent and derivatized with CH3I under microwave irradiation. The methylated barbiturates were separated on a TR-5MS capillary column and detected with an ion trap mass detector. Electron impact ion source (EI) operating MS/MS mode was adopted for identification and external standard method was employed for quantification. One precursor ion m/z 169 was selected for analysis of barbital and amobarbital and m/z 232 was selected for phenobarbital. The product ions were obtained under 1.0 V excitation voltage. Good linearities (linear coefficient R > 0.99) were obtained at the range of 0.5-50 microg kg(-1). Limit of detection (LOD) of barbital was 0.2 microg kg(-1) and that of amobarbital and phenobarbital were both 0.1 microg kg(-1) (S/N > or = 3). Limit of quantification (LOQ) was 0.5 microg kg(-1) for three barbiturates (S/N > or = 10). Satisfying recoveries ranging from 75% to 96% of the three barbiturates spiked in pork were obtained, with relative standard deviations (R.S.D.) in the range of 2.1-7.8%.

Simultaneous determination of phenytoin, barbital and caffeine in pharmaceuticals by absorption (zero-order) UV spectra and first-order derivative spectra--multivariate calibration methods.

The quantitative predictive abilities of partial least squares (PLS-1) and principle component regression (PCR) on absorption (zero-order) UV spectra are compared with the results obtained by the use of these multivariate calibration methods on first-order derivative spectra. Both approaches were satisfactorily applied to the simultaneous determination of these drugs in synthetic and pharmaceutical mixtures. Significant advantages were found in the simultaneous determination of phenytoin, barbital and caffeine in binary and ternary mixtures, by application of different multivariate calibration methods when the calibration matrix was performed using the first-order derivative spectra. The proposed method was validated by applying it to the analysis of binary and ternary mixtures of phenytoin, barbital and caffeine. Determinations were made over the concentration ranges of 0.24-22.0, 0.01-27.0 and 0.049-27.0 microg ml(-1) for phenytoin, barbital and caffeine, respectively, in the binary and 0.45-22.0, 0.05-26.0 and 0.05-20.0 microg ml(-1) for phenytoin, barbital and caffeine, respectively, in the ternary mixtures. The relative standard errors in the determinations were less than 3% in most cases.

[Simultaneous determination of three components in antongding injection by Kalman filtering method].

Kalman filtering method was applied to determine three components in antongding injection without separation. The average recovery and relative standard deviation of amidopyrine, phenazone, barbital obtained by Kalman filtering method were 99.8%, 0.93%, 99.7%, 0.82%, 99.7%, 1.5% respectively. It was showed by t-test that there was no significant difference between the results of Kalman filtering method and standard method.

[The application of solid phase extraction for systematic toxicological analysis of abuse drugs].

A new column was developed in this research. It contains a proprietary bonded silica sorbent that exhibits mixed extraction mechanism. A single-column solid-phase extraction procedure was also developed for the screening of acidic, neutral and basic abuse drugs. The recovery of all 7 tested drugs exceeded 60%. The extraction mechanism for different abuse drugs on the new column was explored and was compared with on other columns. It is suggested that this column be effective in systematic toxicological analysis and better than other columns.

Development of a novel octadecyl-bonded silica column and evaluation of its reliability in chromatographic analysis.

The chromatographic characterization of an octadecyl-bonded silica (ODS) column for high-performance liquid chromatography is described. In general, columns of the same type but obtained from various manufacturers give different chromatographic results, due to differences in the purity of column packings, the properties of the silica gel supports and the density of silanols on the surface of the silica gel. In order to solve this problem and to obtain a high performance ODS column, a series of methods with different samples and conditions were evaluated. The result is important for the optimization of conditions for the synthesis of ODS packings and for minimizing the deleterious effects arising from adsorption activity and metal impurity.

[Quantitative analysis of compound injection of aminopyrine by dual-wavelength linear regression spectrophotometry].

A dual-wavelength linear regression spectrophotometry has been introduced and evaluated. Depending on a group of standard mixture solutions the optimal wavelengths and calibration curve can be determined simultaneously by linear regression method. The deviation of absorption resulting from molecular interaction can be calibrated by this method and the results are more accurate. The validity of this method has been confirmed through its use in the analysis of compound injection of antipyrine with satisfactory recoveries. Results obtained by Kalman filtering (KF), partial least squares (PLS) and target factor analysis (TFA) are also given.

[UV-spectrophotometric analysis of the component of antondin injection by the Monte Carlo method of area fitting].

The Monte Carlo method is a kind of unique calculation method. It can resolve not only the question of define evaluation, but also that of random evaluation. The Monte Carlo area fitting method was applied to UV-spectrophotometry of the multicomponent complex preparations without previous separation. The area of each component of complex preparation within a suitable wavelength range of standard spectrogram was multiplied by certain coefficients, and then the products were obtained to fit the area of the measured multicomponent complex preparations. The method was used to simultaneous determination of barbital, amidopyrine and antipyrine in antondin injection. The experimental data were measured and treated by UV-190 spectrophotometer and microcomputer IBM-PC. The average recoveries of barbital, amidopyrine and antipyrine were 99.1 +/- 1.1% (CV), 99.6 +/- 1.3% (CV), and 99.7 +/- 1.0% (CV), respectively.

Analytical studies on illicit heroin. V. Efficacy of volatilization during heroin smoking.

The recovery of heroin in fumes was investigated. In the Netherlands the common mode of heroin smoking is the 'chasing the dragon' procedure: heroin is heated on an aluminium foil by a lighter and the fumes are inhaled. The efficiency of the volatilization of heroin using this procedure was studied under laboratory conditions using thin layer chromatography, gas chromatography and high pressure liquid chromatography. A considerable influence of the form (salt or base) of the heroin was found as well as strong influences of other substances that may be present in illicit heroin samples as diluents. The danger of the inhalation of fumes containing unknown pyrolysis products is mentioned and a hypothesis is given for the phenomenon of 'heroin'-leucoencephalopathy that was observed in heroin smokers in Amsterdam in 1981. The types of heroin encountered in the Netherlands are discussed with regard to their suitability for smoking.

Optimization of a novel two-phase potentiometric titration method of barbiturates with mercury (II). Part II: Experimental evaluation.

A two-phase potentiometric titration procedure of barbiturates with mercury(II) was developed. The composition of the formed mercury-barbiturate complexes was elucidated by infrared spectrometry. In the new titration procedure the barbituric acid derivative is dissolved in an aqueous borate buffer. An organic phase consisting of chloroform and benzyl alcohol is added, and the vigorously stirred contents of the titration vessel are titrated by a mercury(II) nitrate solution. In the potentiometric determination of the end-point a rotating mercury electrode is used as an indicator electrode that also serves as an efficient stirrer. The two-phase procedure was compared with a one-phase mercurimetric potentiometric titration in borate buffer and with the potentiometric titration by sodium hydroxide in an ethanol-water solution. The proposed two-phase procedure is superior to both methods because lower concentrations of barbiturates (10(-3) - 10(-4) M) can be determined successfully. The one-phase procedure suffers from systematic errors, while the titration with sodium hydroxide is less precise at concentration levels of the barbiturates prevailing in content uniformity studies. By the two-phase procedure the direct titration of phenobarbital and mephobarbital in a dry mix of tablet excipients was possible with a relative standard deviation smaller than 1.5 percent.

[On the polymorphism of barbiturates in powders and tablets. 6: Properties and behaviour of a spray-dried barbital preparation]. / Zur Polymorphie der Barbiturate in Pulvern und Tabletten. 6. Mitteilung: Eigenschaften und Verhalten eines sprühgetrockneten Produktes von Barbital.

The manufacture of a spray-dried barbital preparation is described, the properties, tabletting behaviour and release of which were studied in comparison to the initial substance. Spray-drying led to a compression-resistant mixture of amorphous and crystalline particles. As most of these particles have a spherical shape, the tablets obtained from this mixture were of great compactness, which inhibited the penetration of the medium and, consequently, delayed the release of the drug, too.

[On the polymorphism of barbiturates in powders and tablets. Part 2: On the infrared spectroscopy and the X-ray diffractometry of barbital (author's transl)]. / Zur polymorphie der Barbiturate in Pulvern und Tabletten. 2. Mitteilung: Zur IR-Spektroskopie und Röntgendiffaktometrie von Barbital.

By means of IR spectroscopy and X-ray diffractometry, two commercial brands of barbital and four barbital substances recrystallized from water or an acetone-water mixture were examined for polymorphism. The results obtained demonstrate that these substances differ in crystal lattice and that there are six polymorphic modifications.

Mass spectrometry of medicines. Quantitative determination by direct probe inlet system mass chromatography.

A fundamental study was performed to establish a method of quantitative analysis using mass chromatography by the direct inlet system. The samples were aspirin, phenacetin and caffeine, which are often used as cold medicines, and barbital, allobarbital, phenobarbital and phenytoin which are difficult to analyse by gas chromatography in their intact states. N-acetylsulfamine and ethyl p-aminobenzoate were used as internal standards. Direct inlet mass chromatography was performed by an on-line system of the Shimadzu LKB-9000 and the GC-MSPAC 300. The ratio of the cumulative ions of certain peaks of sample and the internal standard was studied. It was found that, whether the sample is a pure reagent or a mixture, the ratio of cumulative ions of a peak specific to the sample and of a selected peak of the internal standard is proportional to the sample size, the error being less than +/- 3.5% for aspirin, phenacetin and caffeine, and less than +/- 2.7% for barbital, allobarbital and phenobarbital. The same relationship was observed for the phenobarbital and phenytoin mixed in rat plasma, the error being less than +/- 2.0%. It can be concluded that this method is applicable to the quantiative determination of medicines in urine, body fluids and other biological samples.

IR analysis of crystalline samples of some urea derivatives.

The dependence of an IR spectrum of crystal samples of allantoin, barbital, chloroethylaminouracil (dopan), carbromal, 5-allyl-5-(beta-hydroxypropyl)-barbituric acid (ipronal) and theophyllin upon the method of crystals preparation was found after 3 months storage of crystals. There were no differences in the case of mephenytoin. The results obtained here demonstrate the possibility of an occurence of the majority of the analyzed substances as metastable polymorphic modifications in solid dosage forms. Furthermore, the IR identification of drugs requires crystallization of a substance from a particular solvent just before analysis.