Determination of barbiturates by solid-phase microextraction (SPME) and ion trap gas chromatography-mass spectrometry.

Hall BJ, Brodbelt JS.

Department of Chemistry and Biochemistry, University of Texas at Austin 78712-1167, USA.

Solid-phase microextraction (SPME) in conjunction with quadrupole ion trap GC-MS was applied to the determination of a series of barbiturates. A 65 microns Carbowax-divinylbenzene (DVB) SPME fiber was used to successfully extract a series of eight barbiturates from aqueous solution. Absorption kinetics and distribution coefficients for the 65 microns Carbowax-DVB SPME fiber were determined for the compounds. In addition the method was evaluated with respect to linearity, limit of detection, precision, desorption time, and the effect of salt. Limits of detection reached 1 ng/ml for the barbiturates. Linearity was established for the barbiturates over a concentration range of 10-1000 ng/ml, with coefficients of correlation 0.99. Overall, the precision of the method fell between 2.2%-6.5%, depending on the barbiturate. SPME was applied to the identification and quantitation of the barbiturates in a urine matrix. The method was validated by analyzing a reference standard pentobarbital-spiked urine sample. Both standard addition and internal standard with [2H5]-pentobarbital techniques were evaluated, with recoveries found to be 93% and 104%, respectively SPME was then used to rapidly screen a urine specimen tested positive for barbiturates, and butalbital was detected and quantified.

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




Possible interaction between imipramine and butalbital.

Garey KW, Amsden GW, Johns CA.

Clinical Pharmacology Research Center, and Department of Pharmacy, Bassett Healthcare, Cooperstown, New York 13326-1394, USA.

A 44-year-old woman was admitted to the psychiatric unit for exacerbation of her depressive disorder. Blood concentrations of her antidepressant, imipramine, were within normal range and consistent with past concentrations. Her medical history was significant for a chronic headache disorder for which she was given a prescription containing butalbital on admission. The patient's depressive disorder was quickly controlled but relapsed 2 weeks later. Concentrations of imipramine showed a decrease of approximately 50%. Imipramine is metabolized in the liver by the cytochrome P-450 (CYP 1A2) system, and barbiturates are known inducers of this enzyme subset. To our knowledge, an interaction specifically between butalbital and imipramine has not been documented; however, these drugs are extensively prescribed and occasions may arise where they are given concurrently. We recommend repeat measurement of imipramine concentrations 1 week after the start of any butalbital-containing product or barbiturate, and dosage adjustments based on the results and on the patient's response to the change.

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GC/MS confirmation of barbiturates in blood and urine.

Meatherall R.

Laboratory Medicine, St. Boniface General Hospital, Manitoba, Canada.

A gas chromatography-mass spectrometric method is described for the quantitative measurement of 6 commonly used barbiturates in blood and urine specimens. The targeted barbiturates are butalbital, amobarbital, pentobarbital, secobarbital, mephobarbital and phenobarbital. They are recovered along with the internal standard, tolybarb, from blood and urine using liquid extraction then alkalated to form the N-ethyl derivatives. The ethylated barbiturates have symmetrical peaks which are well separated from each other on a non-polar methylsilicone capillary column. The derivatives on a non-polar methylsilicone capillary column. The derivatives facilitate quantitations between 50 and 10,000 ng/mL. The day-to-day CVs for all 6 barbiturates were between 4 and 9% at 200 and 5000 ng/mL. The method has been extended for identifying other acidic drugs and drug metabolites. They are mainly non-steroidal anti-inflammatory drugs, diuretics, and anticonvulsants. An additional 83 compounds can be qualitatively identified.

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




Drug interactions of the components of Optalidon after oral administration.

Lavene D, Longchampt J, Guillaume MF, Kiger JL.

An investigation involving seven successive was undertaken on several groups of 10 to 14 volunteers, in order to evaluate any drug interaction between the three active components of Optalidon, namely amidopyrine (A), butalbital (B), and caffeine (C). Each component was investigated after oral administration, alone and in combination either with one of the others (i.e. A+B, B+C, C+A) or with both of the others in Optalidon (A+B+C). The plasma concentration and urinary excretion were recorded for each component as a function of time. For amidopyrine, two metabolites, amino-4-antipyrine and acetamino-4-antipyrine, were also measured in the urine. Based on a pharmacokinetic model, the following conclusions can be drawn: a) There is no change in bioavailability due to the combination of the three components in Optalidon in respect to their single administration. Within each study, there is no significant difference between the elimination rate constants, areas under the plasma concentration/time curve and percentage excreted in urine for the three components administered alone or in any combination with the other components of Optalidon. b) Concerning the absorption half-life, there is no change for amidopyrine. Only caffeine and butalbital show a statistically significant interaction in respect to this parameter and, as a consequence, differences in the time and value of the maximal plasma concentration in Optalidon. However, these differences are scarcely of anyl clinical relevance.

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Supercritical fluid extraction and negative ion electrospray liquid chromatography tandem mass spectrometry analysis of phenobarbital, butalbital, pentobarbital and thiopental in human serum.

Spell JC, Srinivasan K, Stewart JT, Bartlett MG.

Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens 30602-2352, USA.

Four commonly used barbiturates (phenobarbital, butalbital, pentobarbital and thiopental) were analyzed in human serum using supercritical fluid extraction (SFE) and negative ionization LC/ESI-MS/MS. Barbital was used as the internal standard. Carbon dioxide SFE was performed at 40 degrees C and 500 atm, with a total extraction time of 35 min. The analytes were collected off-line in a liquid trap containing absolute methanol. Samples were then concentrated by vacuum centrifugation. The high performance liquid chromatography separation utilized gradient elution with a total analysis time of 21 min. The precursor and major product ions for the four barbiturates were monitored on a triple quadrupole mass spectrometer with negative ion electrospray ionization (ESI) in the multiple reaction monitoring mode as follows: (1) thiopental (m/z 241.20-->58.00), (2) phenobarbital (m/z 231.10-->188.0), (3) pentobarbital (m/z 225.10-->181.90) and (4) butalbital (m/z 222.80-->179.90). In the case of phenobarbital, pentobarbital and butalbital, the most abundant product ion arises from the loss of 43 u (HCNO loss). However, in the case of thiopental, the most abundant product ion was observed at m/z 58.0 (the [M-183]-ion, or NCS-). Mechanisms for the formation of the collision induced dissociation reaction products of these barbiturates are proposed.

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