Chlorpromazine Ethanol

For the in vitro test, the fibroblasts are allowed to form a half-confluent monolayer within 24 h. Different concentrations of the test chemical are then incubated for 1 h with two sets of cells in parallel (typically on 96-well plates, 104 cells per well, passage number <100). After the incubation with the test substances, one set is irradiated with a nontoxic dose of UVA light (5 J/cm2), while the other set is kept in the dark. Twenty hours after irradiation, cell viability is evaluated by measuring the uptake of NR for 3 h. After the end of the absorption process, excess NR is removed and the cells are treated with an NR desorption solution (ethanol/acetic acid) to extract the dye taken up by the cells. Subsequently, the optical density of the NR solution is measured at 540 nm. As positive control, a test with chlorpromazine is performed. 

Chlorpromazine hydrochloride is soluble to the degree of 1 part in 0.4 parts of water, 1 part in 1.3 parts of alcohol, 1 part in 1 part of chloroform, and practically insoluble in ether [4]. It has also been reported to be soluble in methanol, ethanol, and chloroform, and to be practically insoluble in ether and benzene [3],... 

UV spectroscopic studies of chlorpromazine hydrochloride were conducted in ethanol and water solutions, and the resulting spectra are shown in Figure 3. The data were obtained between 200 and 345 nm using a Shimadzu 1601 PC UVA IS spectrophotometer (Figure 3). 

The British Pharmacopoeia has adopted the assay of chlorpromazine in acetone, using a non-aqueous titration with perchloric acid and methyl orange as the indicator [4], According to the described procedure, each mL of 0.1 M perchloric acid is equivalent to 0.03189 g of drug substance. For chlorpromazine hydrochloride, the BP has described its titration with NaOH in a 1 10 solution of 0.01 M HCl / ethanol. Determining the end point potentiometrically, each mL of 0.1 M sodium hydroxide is equivalent to 0.03558 g of substance. 

Chlorpromazine was determined by diluting 5 mL of a 0.01 M solution with 25 mL of H2O and 20 mL of ethanol, and titrating to a conductimetric endpoint with 0.05N acid or 0.05 N NaOH [63]. Chlorpromazine was determined by titration with KBr03, NaN03, or Ce(S04)2, the determination being made with the use of a molybdenum anode and a graphite, platinum, or tungsten cathode [64]. 

Chlorpromazine formed an insoluble 1 1 complex with lead picrate, and 5 3 complexes with the picrates of cadmium, copper, and zinc [70]. The sample (0.1 g) was dissolved in 15 mL of 95% ethanol, and the solution adjusted to pH 9 with 0.1 N NaOH. After adding 25 mL of a 0.02 M picrate reagent (30 mL of Pb), the solution was set aside for 2 hours. The precipitate was collected on a sintered glass fuimel, and the unconsumed metal in the filtrate was titrated directly with 0.02M EDTA at pH 10.4 (after adding 0.5 g of potassium sodium tartrate for Pb). Eriochrome black T was used as the indicator. 

Tablets containing chlorpromazine and promethazine were powdered and dissolved in 95% ethanol. The absorbance of a 6 pg/mL solution was measured at 6 wavelengths, and the amount of each component calculated by a least squares method [85]. A spectrophotometric method for the simultaneous determination of 1-18 mg of chlorpromazine hydrochloride and 3-27 mg of promethazine hydrochloride (in 20 mM HCl) was presented, where the absorbance was measured over a spectral region of 275-240 nm [86].

Iwaoka T, Kondo M. Mechanistic studies on the photooxidation of chlorpromazine in water and ethanol. Bull Chem Soc Jap 1974 47(4) 980-986. 

The most lethal compound in this assay was chlorproma-z.inc. with a BR (LDuxi) of only 0.0(HXX)63I mmol and the least active was ethanol, with a BR of 0.087096 mmol. In other words, it takes about 13.800 times as many millimolc,s of ethanol than of chlorpromazine to kill l(X)% of the test subjects in this particular assay. 

Now. let s. see if the data can he linearized by using the logiuithms of the biological activity and partition coefficient. Notice that as logarithmic tenns. the difference between the LDiiai of chlorpromazine and ethanol is only 4.14 logarithmic units.. Similarly, the difference between ehlorproma-... 

Fiq. 35. A chromatogram of an ether extract (see text) of 5 ml of urine containing 0.5 /ig each of imipramine, promazine, chlorpromazine, and mepazine per milliliter of urine. Residue was dissolved in 100 /d of ethanol 5 /tl of this solution was injected into the gas chromatograph. Column temperature 240° attenuation X 20. Reproduced from Street (Sll) with permission. 

The patient is experiencing symptoms of the withdrawal syndrome from physical dependency on ethanol. Since seizures are possible, it would not be appropriate to attempt sedation with a phenothiazine such as chlorpromazine. Thiamine is usually administered to counteract the symptoms of Wernicke-Korsakoff syndrome but will not alleviate withdrawal symptoms. Neither buspirone nor naltrexone has value in the immediate management of alcohol withdrawal states. The patient is indeed suffering from delirium tremens. The answer is (B). 

Some active substances or excipients have an antimicrobial effect not only through reducing the water activity, but also through a specific antimicrobial mechanism. The best-known example is propylene glycol, but also ethanol, local anaesthetics, chlorpromazine hydrochloride, promethazine hydrochloride and essential oils exhibit a specific antimicrobial effect. In addition, the combination of weak antimicrobial effects of disodium edetate, borax, and boric acid appeared to justify prolongation of the shelf life of non-preserved eye drops over the standard limit of 24 h [48]. 

Figure 4.19 The stabilizing and lytic effects of various tranquilizers and antihistamines on human erythrocytes. Stabilization of the erythrocytes against hypotonic haemolysis is caused by butyrylperazine dimaleate, prochlorperazine ethane disulphonate, fluphenazine diHCl, reserpine phosphate, thioridazine HCl, trifluoperazine diHCl, chlorpromazine HCl, promethazine HCl, and haloperidol. High concentrations of all the compounds caused direct lysis. Stabilization by chlorpromazine sulphoxide occurred at concentrations higher than equiosmolar concentrations of NaCl or sucrose. All the compounds were dissolved in aqueous solution except haloperidol which was added to the final aqueous solution from concentrated stock ethanolic solutions. The final concentration of the erythrocytes was 2.4 x 10 cells ml A relative haemolysis of 1.0 indicates an absolute degree of haemolysis of around 40%. From Seeman and Weinstein [158] with permission.

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