Disulfiram (Antabuse) produces a sensitivity to alcohol which results in a highly unpleasant reaction when the patient under treatment ingests even small amounts of alcohol. Disulfiram blocks the oxidation of alcohol at the acetaldehyde stage. Accumulation of acetaldehyde (5 to 10 times higher than that found during metabolism of the same amount of alcohol alone) in the blood produces a complex of highly unpleasant symptoms referred to as the disulfiram-alcohol reaction: flushing, throbbing in head and neck, respiratory difficulty, nausea, copious vomiting, palpitation, tachycardia, vertigo, blurred vision and confusion. Bupropion (Zyban) is used mainly as an antidepressant, but also as an aid to smoking cessation with motivational support in nicotine-dependent patients. Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine, and does not inhibit monoamine oxidase or the re-uptake of serotonin. The mechanism by which Zyban enhances the ability of patients to abstain from smoking is unknown. However, it is presumed that this action is mediated by noradrenergic and/or dopaminergic mechanisms. A specific and reproducible HPLC method coupled with Diode Array Detection (DAD) has been developed to simultaneously quantify Disulfiram and Bupropion in human plasma. The analysis was performed on an reversed-phase C8 column, with a mobile phase consisting of a mixture of phosphate buffer and acetonitrile (55/45). DAD detection was carried out at 250 nm. The assay showed a linear response for Disulfiram (5-1000 ng/mL) and for Bupropion (2.5-1000 ng/mL). A careful and rapid solid-phase extraction (SPE) procedure on C2 cartridges was chosen for plasma sample purification and pre-concentration obtaining good extraction yield values for each analyte. Assays are currently underway to validate the method and to apply it to determination of Disulfiram and Bupropion in plasma samples from alcohol and nicotine-dependent patients.
Simultaneous HPLC analysis of deterrent drugs, disulfiram and bupropion, in human plasma / M.A. Saracino; F. De Stefano; C. Iannello; A. Ferranti; M. Amore; M.A. Raggi. - STAMPA. - (2007), pp. 159-159. (Intervento presentato al convegno RDPA 2007, 12th Meeting on Recent Developments in Pharmaceutical Analysis tenutosi a Isola d'Elba nel September 23-28).
Simultaneous HPLC analysis of deterrent drugs, disulfiram and bupropion, in human plasma
SARACINO, MARIA ADDOLORATA;IANNELLO, CARMELINA;FERRANTI, ANNA;RAGGI, MARIA AUGUSTA
2007
Abstract
Disulfiram (Antabuse) produces a sensitivity to alcohol which results in a highly unpleasant reaction when the patient under treatment ingests even small amounts of alcohol. Disulfiram blocks the oxidation of alcohol at the acetaldehyde stage. Accumulation of acetaldehyde (5 to 10 times higher than that found during metabolism of the same amount of alcohol alone) in the blood produces a complex of highly unpleasant symptoms referred to as the disulfiram-alcohol reaction: flushing, throbbing in head and neck, respiratory difficulty, nausea, copious vomiting, palpitation, tachycardia, vertigo, blurred vision and confusion. Bupropion (Zyban) is used mainly as an antidepressant, but also as an aid to smoking cessation with motivational support in nicotine-dependent patients. Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine, and does not inhibit monoamine oxidase or the re-uptake of serotonin. The mechanism by which Zyban enhances the ability of patients to abstain from smoking is unknown. However, it is presumed that this action is mediated by noradrenergic and/or dopaminergic mechanisms. A specific and reproducible HPLC method coupled with Diode Array Detection (DAD) has been developed to simultaneously quantify Disulfiram and Bupropion in human plasma. The analysis was performed on an reversed-phase C8 column, with a mobile phase consisting of a mixture of phosphate buffer and acetonitrile (55/45). DAD detection was carried out at 250 nm. The assay showed a linear response for Disulfiram (5-1000 ng/mL) and for Bupropion (2.5-1000 ng/mL). A careful and rapid solid-phase extraction (SPE) procedure on C2 cartridges was chosen for plasma sample purification and pre-concentration obtaining good extraction yield values for each analyte. Assays are currently underway to validate the method and to apply it to determination of Disulfiram and Bupropion in plasma samples from alcohol and nicotine-dependent patients.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
