GLC-mass spectrometric procedure with selected-ion monitoring for determination of plasma concentrations of unlabeled and labeled barbital following simultaneous oral and intravenous administration.

Varin F, Marchand C, Larochelle P, Midha KK.

A GLC-mass spectometric method employing specific-ion monitoring was developed for the determination of plasma concentrations of labeled (15N1,3, 13C2) and unlabeled barbital following simultaneous intravenous and oral administration. This method proved to be more sensitive and precise than the method employing GLC with flame-ionization detection or GLC with alkali flame-ionization detection. After extraction of [15N1,3, 13C2]barbital, barbital, and the internal standard, butalbital, from plasma with ether, the organic solvent is evaporated, and the labeled and unlabeled drug as well as the internal standard are converted into their N,N-dimethyl derivatives by treatment with diazomethane. The excess reagent is evaporated, and the resulting methyl derivatives are analyzed by GLC-mass spectrometry with selected-ion monitoring. The method is sufficiently sensitive to determine 0.5 microgram of the labeled and unlabeled drug/ml with a relative standard deviation of less than 5%. The application of the method to the determination of the plasma concentration of labeled and unlabeled drug over 6 days following simultaneous oral and intravenous administration of a single dose is demonstrated.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=&dopt=Abstract butalbital fioricet barbiturate




Anion mass spectrometry of barbiturates.

Jones LV, Whitehouse MJ.

Recent trends towards increasing abuse of the barbiturates has led to a proposal to legally restrict some of them. The implementation of the resulting legislation might require specific identification of the barbiturates. Such identification is not readily available from electron impact mass spectra and, even when these are supplemented with chemical ionization data, barbiturates differing only in isomeric sidechains are not completely characterized. In this study the anion mass spectra of 30 barbiturates, including all of those commonly available, are presented. The spectra are simple; ions arising from hydrogen atom and sidechain elimination from the initially formed [M]- ion are diagnostic of the barbiturate. For all but two of the barbiturates (butalbital and idobutal) relative peak intensities will discriminate between barbiturates differing only in isomeric sidechains.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=&dopt=Abstract butalbital fioricet barbiturate




Rapid method for screening toxic drugs in serum with liquid chromatography.

Kabra PM, Stafford BE, Marton LJ.

We present a method for the simultaneous analysis of a variety of commonly abused drugs (acetaminophen, theophylline, salicylate, primidone, methyprylon, phenobarbital, butabarbital, ethchlorvynol, butalbital, chlordiazepoxide, pentobarbital, amobarbital, phenytoin, glutethimide, secobarbital, flurazepam, nitrazepam, methaqualone, N-desmethyldiazepam, and diazepam) in serum or plasma. Serum proteins are precipitated with an acetonitrile solution containing hexobarbital, the internal standard. The drugs are eluted from a reversed-phase column with a mobile phase consisting of acetonitrile/phosphate buffer (pH 3.2), using a two-step linear gradient, at a flow rate of 3.0 mL/min. The eluted drugs are detected by their absorption at 210 nm; their quantities are estimated from their peak heights. A complete analysis requires no longer than 45 minutes at the optimum column temperature of 50 degree C. A sensitivity of 2 mg/L of serum is attained routinely for most of the hypnotic and analgesic drugs; while methaqualone, chlordiazepoxide, diazepam, and N-desmethyldiazepam can be detected at a concentration of 0.2 mg/L. Analytical recoveries for the twenty drugs varied from 93-112%, with good reproducibility. Of more than forty drugs tested for possible interference, desmethyldoxepin, procainamide, phenylpropanolamine, mesantoin, and phenacetin interfere with the analysis of flurazepam, acetaminophen, ethchlorvynol, and phenobarbital, respectively.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=&dopt=Abstract butalbital fioricet barbiturate




Application of micellar electrokinetic capillary chromatography to forensic analysis of barbiturates in biological fluids.

Ferslew KE, Hagardorn AN, McCormick WF.

Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, USA.

Micellar electrokinetic capillary chromatography (MECC) is a form of capillary zone electrophoresis. Addition of a surfactant produces micelles in an aqueous/organic buffer. Separation of drugs is obtained via differences in the electrophoretic mobilities of the analytes within the capillary, resulting from their electrophoretic velocity and the electroosmotic flow of the buffer in a given electric field. The migration order is determined by the differential partitioning of the drugs between the micelles and the aqueous/organic phase. Barbiturates were extracted from various biological fluids at pH 4.5 with TOXI-TUBES B. MECC analyses were performed using a Waters Quanta 4000 Capillary Electrophoretic System with a 745 Data Module with a 75 microns x 60 cm capillary and an aqueous/organic buffer of 85% 10 mM borate, 10 mM phosphate, 100 mM sodium dodecyl sulfate and 15% acetonitrile at a pH of 8.5 with a voltage of 20 kV using ultraviolet absorption detection at 214 nm. Migration times were: phenobarbital, 7.78 min.; butalbital, 8.01 min.; butabarbital, 8.23 min.; mephobarbital (internal standard), 8.88 min.; amobarbital, 9.41 min.; pentobarbital, 10.03 min. and secobarbital, 10.79 min. Correlation coefficients (r) between peak areas and concentration ranges of 3 to 60 micrograms/mL were from 0.964 to 0.999. Coefficients of variation (CV) ranged from 2.6 to 8.6% between days and 2.3 to 9.8% within day. Application of this methodology to four forensic cases of butalbital intoxication detected concentrations of 0.7 to 12.7 micrograms/mL in blood; 0.8 to 1.9 micrograms/mL in vitreous humor and 1.5 to 7.6 micrograms/mL in urine. MECC is applicable to forensic analysis of barbiturates extracted from biological fluids.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=&dopt=Abstract butalbital fioricet barbiturate




Improved gas chromatography/mass spectrometry analysis of barbiturates in urine using centrifuge-based solid-phase extraction, methylation, with d5-pentobarbital as internal standard.

Liu RH, McKeehan AM, Edwards C, Foster G, Bensley WD, Langner JG, Walia AS.

Department of Criminal Justice, University of Alabama at Birmingham.

Effective solid-phase extraction, derivatization, and GC/MS procedures are developed for the simultaneous determinations of butalbital, amobarbital, pentobarbital, and secobarbital, using a deuterated pentobarbital (d5-pentobarbital) as the internal standard. Buffered (pH 7) urine samples were extracted with Bond Elute Certify II cartridge. Iodomethane/tetramethylammonium hydroxide in dimethylsulfoxide was used for methylation, while a HP 5970 MSD equipped with a 13 m J & W DB-5 column (5% phenyl polysiloxane phase) and the Thru-Put Target software package were used for GC/MS analysis and data processing. This protocol was found to be superior, in both chromatographic performance characteristics and quantitation results, over a liquid-liquid extraction procedure without derivatization using hexobarbital as the internal standard. Extraction recoveries observed from control samples containing four barbiturates range from 80% to 90%. Good one-point calibration data are obtained for all four barbiturates in the 50 to 3200 ng/mL range. Interestingly, the one-point calibration data for pentobarbital are inferior to the other three barbiturates--due to interference from the internal standard (d5-pentobarbital). The calibration data of pentobarbital are best described by a hyperbolic curve regression model. Precision data (% CV) for GC/MS analysis, over-all procedure, and day-to-day performance are approximately 2.0%, 6.0%, and 8.0%, respectively. With the use of a 2 mL sample size, the attainable detection limit is approximately 20 ng/mL.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=&dopt=Abstract butalbital fioricet barbiturate