Column liquid chromatography of tricyclic antidepressants

A column liquid chromatographic system for the analysis of tricyclic antidepressants in serum is described. A high separation efficiency can be obtained with a mixture of ethyl acetate, n-hexane and methylamine as eluent on a silica gel column. The retention is easily regulated by varying the concentration of n-hexane, the modifier methylamine and the water content of the ethyl acetate. Examples are given of separation of test mixtures of tricyclic antidepressants and of some of these drugs in serum. UV detection permits determinations down to the 10-ng level in serum.     

Stability of tricyclic antidepressants in formalin solutions

We investigated the stability of the secondary amines, desipramine (DP) and nortriptyline (NRT), and the tertiary amines, imipramine (IP) and amitriptyline (AT), in formaldehyde (F) and paraformaldehyde (PF) aqueous solutions. NRT showed little instability in 0.37 to 37% F and PF solutions, but AT formation was detected and increased, up to 0.46 to 2.7%, in parallel with rising F and PF concentrations. DP was unstable and levels decreased to 74 to 96% with increasing F concentrations, and fell only to 96% in 10% PF solution. IP formation increased in the same manner as AT to 2.9 to 3.5% of the initial DP. When AT and IP were stored in F and PF solutions, concentrations of AT and IP did not change. DP in F pH 3 to 11 phosphate buffer (PB) solutions showed high recovery in the order: pH 5 > pH 7 > pH 9 > pH 3 and pH 11. DP in PF buffered solutions decreased slightly only at pH 3 (3.5%). By contrast, IP did not change at any pH (pH 3 to 11) of the F or PF solutions. During storage for 21 days at room temperature in 3.7% F and PF solutions, IP and DP degradation was accelerated when compared with the values in pH 3 and 7 PB solutions. However, IP detected in DP F or PF solution was only 0.2% of the initial DP 21 days after storage. Thus, AT, NRT, IP and DP degraded gradually in F and PF solutions during storage at room temperature. TCAs may first react nucleophilically with formaldehyde to form hemiaminals. DP in 3.7% formaldehyde aqueous solution formed little of its methylated product, IP, at room temperature.     

Acute lung failure induced by tricyclic antidepressants

The determination of the naphthodianthrone constituents in extracts of dried blossoms of Hypericum perforatum L. by combined HPLC-electrospray mass spectrometry is described. Hypericin (1), pseudohypericin (2) and their precursor compounds produce intensive negative quasi-molecular ions by deprotonation provided a non-acidic eluent system is used in the HPLC separation. From the [M-H]- ions formed in the electrospray ionization process characteristic daughter ion spectra can be obtained by collisional activation which have been studied by tandem mass spectrometry.     

Augmentation of pentylenetetrazol induced seizures by tricyclic antidepressants

The effect of a brief appointment reminder for mental-health center applicants is reported. A standardized phone message was delivered by an administrative staff member one to three days before the appointment and a sequential experimental design alternating baseline and phone message conditions was used to assess the effects of the procedure. The no-show rate averages were 32%, 11%, 25%, and 14% respectively. The cost of the procedure was $162.00, which was totally recovered when only six appointments were kept. Since over 1000 patients were involved in the study, the return on the investment of +162.00 is considerable. Implications for this procedure are discussed for other community mental-health centers and for other community care-giving agencies.     

Column deactivation in analysis for underivatized tricyclic antidepressants by gas chromatography with use of a nitrogen detector

I describe deactivation treatment of the OV-17 chromatographic column to minimize adsorption of tricyclic antidepressant drugs on the solid support of the column. The procedure involves heat treatment at 399 degrees C under a low flow of nitrogen, with bleeding of OV-17 liquid phase from the injector tube into the column. The column is then conditioned with vapors of phenyldiethanolamine succinate, added to the carrier gas stream by bleeding from a coated injector glass tube. This deactivation process much improves the chromatographic performance of the column, allowing a sensitivity at the nanogram level with a nitrogen-sensitive detector. Determinations of tricyclic antidepressants in plasma with such a deactivated column results in a low CV and a linear calibration curve, reflecting the effectiveness of the deactivation.     

The use of tricyclic antidepressants in children and adolescents

For children and adolescents, TCAs have proven efficacy in the treatment of enuresis, OCD, and ADHD, with less compelling evidence in anxiety and tic disorders and as-yet unproven efficacy in major depression. The TCAs continue to be a valuable second-line treatment in the previously mentioned conditions. Given the possible adverse effects caused by these medications and the individual variability in plasma levels, effective, responsible use of these medications includes careful monitoring by the prescribing clinician.     

Severe bradyarrythmia induced by tricyclic antidepressants in an elderly patient

The fluoroquinolones have an established role in treatment of infection with aerobic gram negative rods. The increased importance of gram positive nosocomial infection and of acquired fluoroquinolone resistance has stimulated a search for new compounds with enhanced potency and spectrum. CP-99,219 is a novel compound in this class with enhanced activity against gram positive organisms. We have studied the activity of CP-99,219 relative to ciprofloxacin, fleroxacin, ofloxacin, and sparfloxacin using test panels of organisms with a high proportion of ciprofloxacin resistance. CP-99,219 is more potent than any of the other four compounds against both gram positive and gram negative bacteria. The activity of CP-99,219 against many bacteria resistant to the established agents, warrants further in vitro and clinical studies.     

A case of allergic cross reaction between tricyclic antidepressants and maprotiline

Although a 76-year-old woman with a diagnosis of depression began a course of maprotiline, the drug was discontinued after 14 days when she developed a rash. She was started on lofepramine in substitution for maprotiline. Four years later, lofepramine treatment was stopped and to amoxapine treatment introduced due to the aggravation of depressive symptoms. On the second day of this regimen, she developed a pruritic rash. She stopped the medication immediately. Because the rash disappeared gradually, lofepramine treatment was restarted. But her recovery was restrained and new skin lesions developed. Again, she stopped the medication, and the rash cleared within several days. This case suggests the existence of cross-allergenicity between tricyclic antidepressants and maprotiline.     

Fluoxetine and tricyclic antidepressants: clinical tolerance in short-term combined administration

No-carrier-added racemic [11C]metaraminol was prepared by a selective condensation of [11C]nitroethane with 3-hydroxy-benzaldehyde using tetrabutylammonium fluoride in tetrahydrofuran (THF) as a catalyst, followed by a reduction with Raney nickel in formic acid. [11C]Metaraminol was produced in 30 to 45% decay-corrected yield from [11C]nitroethane (13 to 20% decay corrected from [11C]CO2) within 45 to 55 min total synthesis time. Reversed phase high-performance liquid chromatography (HPLC) was used for the separation of the racemic erythro- and threo-forms of [11C]metaraminol. The radiochemical purity was higher than 98%, and the specific radioactivity at the end of synthesis was 500 to 800 Ci/mmol (18 to 30 GBq/mumol). Positron emission tomography (PET) examination of racemic erythro-[11C]metaraminol in a Cynomolgus monkey showed a high uptake of radioactivity in the heart. Following pretreatment with the selective norepinephrine reuptake inhibitor desipramine, the radioactivity uptake in the myocardium was markedly reduced (80%), demonstrating the specificity of erythro-[11C]metaraminol for the norepinephrine reuptake system of the heart. Pretreatment with desipramine had no effect on radioactivity in lung. The metabolism was rapid for [11C]metaraminol. The amounts of the total radioactivity representing [11C]metaraminol in plasma, determined by HPLC, were 14% at 6 min and 8% at 34 min. The high specific uptake of racemic erythro-[11C]metaraminol indicates that enantiomerically pure (R,S)-[11C]metaraminol has potential for detailed mapping of the sympathetic innervation of the human myocardium.     

The use of phenothiazines and tricyclic antidepressants in the treatment of intractable pain

The use of trifluoperazine and amitriptyline in the treatment of pain is described. Of 12 patients who were suffering chronic pain from various causes, 8 obtained a major degree of relief from the use of this combination of drugs.     

Capillary electrophoretic separation of tricyclic antidepressants using charged carboxymethyl-beta-cyclodextrin as a buffer additive

Charged carboxymethyl-beta-cyclodextrin was successful in the capillary electrophoretic separation of a series of tricyclic antidepressants. The cyclodextrin alone was successful in the separation of carbamazepine, protriptyline, desipramine, clomipramine, and opipramol using a 3-(trimethoxysilyl)propyl methacrylate capillary coating to reduce the electroosmotic flow. The ideal buffer pH was found to be in the range of 6-7 and the ideal cyclodextrin concentration to be 10 mM. All nine antidepressants were resolved using the charged cyclodextrin in the micellar electrokinetic chromatography (MEKC) mode with sodium dodecyl sulfate as the surfactant. Neither the cyclodextrin nor the surfactant alone were successful in resolving the whole series of compounds under investigation but a combination of both produced the separation. Separations were performed on a linear polyacrylamide coated capillary. The ideal pH of the buffer was in the range of 5-7.