Use of a statistically designed experimental approach to optimize the propylketal derivatization of barbiturates.The derivatization of barbiturates with dimethylformamide dipropylacetal and dimethylformamide diisopropylacetal is studied with respect to the optimization of reaction recovery and reliability. A second-order orthogonal experimental design is utilized in order to obtain regression equations for the reaction recovery dependence on the derivatization solution composition, incubation temperature, and time for amobarbital, Butalbital ( Fioricet ), pentobarbital, phenobarbital, and secobarbital. Regression equations for the effect of incubation temperature and time on the derivative recovery and the optimum conditions for derivatization recoveries are obtained. Differences in the phenomena of the derivative formation are evaluated between the two derivatizing reagents and the barbiturates. Based on the analysis of the obtained equations, it is concluded that the dipropylketal derivative of barbiturates is superior in comparison with diisopropylketal when considering the milder conditions of the reaction, absence of sudden changes in the recovery with a variation in the derivatization parameters, and reliability for the simultaneous testing of the barbiturates. A method for the routine testing of the barbiturates by gas chromatography-mass spectrometry in urine specimens is included.
Application of atmospheric pressure chemical ionisation mass spectrometry in the analysis of barbiturates by high-speed analytical countercurrent chromatography.Four barbiturates (barbital, allobarbital, phenobarbital and Butalbital ( Fioricet )) were analysed using high-speed analytical countercurrent chromatography (HSACCC) and high-performance liquid chromatography (HPLC) interfaced with mass spectrometry, using negative mode atmospheric pressure chemical ionisation (APCI). The polar biphasic solvent system of butyronitrile/acetonitrile/water (1:1:1) was used, in the upper-stationary, lower-mobile mode of operation, at a flow rate of 1 mL/min and a rotational speed of 1200 rpm, equating to an applied "g"-field of 177 g. The fractional stationary phase retention (S(F)) was 0.58. Representative mass spectral data are presented from the HPLC and the HSACCC analyses. Structural information was obtained using source-induced fragmentation at increased source block voltages. The effect of increasing g-field on chromatographic resolution is illustrated using the binary base system of butyronitrile/water (1:1), under electrospray ionisation. Copyright 2003 John Wiley & Sons, Ltd.
Severe barbiturate withdrawal syndrome in migrainous patients.Three patients who presented with grand mal seizures and an associated behavioral disorder were recognized as suffering from a severe Butalbital ( Fioricet ) withdrawal syndrome. All were migraineurs who had become dependent on barbiturates. We propose that the occurrence of seizures, psychotic behavior, or a recent personality change should be considered clues to possible barbiturate abuse in patients with migraine.
Mechanistic studies on the use of 2H- and 13C-analogues as internal standards in selected ion monitoring GC-MS quantitative determination--Butalbital ( Fioricet ) example.As a part of our study on the use of isotopic analogues as the internal standard (IS) for the quantitation of drug analytes, this article reports on the performance characteristics of 2H5-Butalbital ( Fioricet ) and 13C4-Butalbital ( Fioricet ) with particular focus on (1) determining and comparing the effectiveness of the 2H- and 13C-analogues in serving as the ISs for quantitation; (2) understanding the "cross-contribution" phenomenon underlying the effectiveness of selected ion pairs used for quantitation purpose; and (3) examining whether the same characteristics, observed in our preliminary report for the secobarbital/2H5-secobarbital/13C4-secobarbital system, also exist in the Butalbital ( Fioricet )/2H5-Butalbital ( Fioricet )/13C4-Butalbital ( Fioricet ) system. Adapting similar procedures applied to our previous study on the secobarbital system, we observed that (1) both labeled analogues (13C4-Butalbital ( Fioricet ) and 2H5-Butalbital ( Fioricet )) cause more significant cross-contributions to ions designated for Butalbital ( Fioricet ) than Butalbital ( Fioricet ) to the labeled analogues; (2) compared to 2H5-Butalbital ( Fioricet ), 13C4-Butalbital ( Fioricet ) appears to cause less cross-contributions to ions designated for Butalbital ( Fioricet ); (3) cross-contribution between the following ion pairs are minimal: m/z 200/196, 199/195, 185/181 (13C4-Butalbital ( Fioricet ) as the IS) and m/z 201/196 (2H5-Butalbital ( Fioricet ) as the IS). It is also concluded that the Butalbital ( Fioricet )/2H5-Butalbital ( Fioricet ) system exhibits the same concentration dependency phenomenon observed in the secobarbital/ 2H5-secobarbital system, that is, ratios of ion pairs designated for these two isotopic analogues (resulting from routine gas chromatography-mass spectrometry protocol) increase as their concentrations are diluted. (In parallel with the secobarbital/13C4-secobarbital system, the Butalbital ( Fioricet )/13C4-Butalbital ( Fioricet ) system does not exhibit this phenomenon.)
Efficacy and safety of sumatriptan 50 mg in patients not responding to standard care, in the treatment of mild to moderate migraine. The Sumatriptan 50 mg Italian Study Group.The tolerability and efficacy of oral sumatriptan 50 mg for the treatment of mild to moderate migraine attacks were assessed in a double-blind, multicenter placebo-controlled study on a group of patients who had not responded sufficiently to analgesic preparations. Three-hundred-and-twenty-eight migraine sufferers treated a first migraine attack with a nontriptan standard care medication: a mixture containing phenazone, Butalbital ( Fioricet ) and caffeine (optalidon) or indomethacin plus prochlorperazine plus caffeine (difmetre) or paracetamol 100 mg (tachipirine), depending on their habits. Of these patients, 32.6% reported headache relief with this treatment and were not included in phase II of the study. The 219 patients not reporting relief during the first phase of the study entered the second phase and were randomized to sumatriptan 50 mg or to placebo; 167 of these patients treated a second attack according to the protocol and were evaluated for efficacy. Of the patients with migraine taking sumatriptan, 58% reported headache relief compared with 35% of placebo-treated patients (p = 0.008). The reduction of nausea and vomiting was significantly better in the sumatriptan group. No differences were detected for the recurrence rate, while rescue medication was used more by the placebo group. The safety profile of sumatriptan 50 mg was confirmed. This study demonstrates the usefulness of this dose of oral sumatriptan against the pain and the accompanying symptoms of mild and moderate migraine.
Migraine headache misconceptions: barriers to effective care.Migraine headaches affect 12% of the adult population in the United States and cause a significant economic loss due to decreased workplace productivity. Although interactions between pharmacists and individuals with headache are common, few pharmacists receive adequate training regarding migraine therapy. We refute several misconceptions that hinder effective care, such as that migraine is a vascular disease, triptans cause rampant cardiac-related morbidity and even mortality, a best oral triptan exists, sinus and tension headaches are prevalent, and migraine is a minor economic problem. Our pathophysiologic understanding demonstrates that migraine is a neurologic process of the trigeminovascular system, of which vascular effects are secondary. This process can result in a myriad of clinical signs and symptoms, often leading to a misdiagnosis of sinus or tension headache. The last decade's experience with triptans in more than half a billion people worldwide reveals a benign adverse-effect profile, particularly when taken early in an attack. Published reports and real-world experiences illustrate that these drugs do not merit fears of triptan-induced cardiac consequences in appropriately selected individuals. Society's productivity loss due to migraine is measured in billions of dollars. Restoring a patient's ability to function normally is now recognized as the primary treatment goal, not merely relieving pain. Thus, the overreliance on "pain killer" drugs such as Butalbital ( Fioricet )-containing products and the continued underutilization of migraine-specific drugs need to be addressed. Opportunities exist for pharmacists and other health care providers to dispel continually propagated migraine misconceptions and familiarize themselves with advances in therapy. Such actions will benefit patients, the health care system, and society as a whole. Comment: This is a marvelous review for residents and primary care practitioners.-Stewart J. Tepper This is a thought provoking article which deserves to be widely discussed. It contains many home truths which should have considerable impact for health care practitioners and will provide useful ammunition for patient groups and headache physicians battling to access resources for headache patients. We reached similar conclusions following our U.K. population survey of headache treatment and health care utilization. Undoubtedly, pharmacists and other health care professionals can act as important conduits to facilitate the prompt effective treatment of headache.