Extraction and determination of trace amounts of chlorpromazine in biological fluids using magnetic solid phase extraction followed by HPLC

A simple, rapid and sensitive method termed as magnetic solid phase extraction （MSPE） combined with high-performance liquid chromatography-ultraviolet detector （HPLC-UV） has been proposed for the determination of trace amounts of chlorpromazine （CPZ） in water, urine and plasma samples. The separation and determination was performed on a C18 column under the optimal chromatographic conditions. Several factors influencing the extraction efficiency of CPZ, such as pH, surfactant and adsorbent amounts, ionic strength, extraction time, sample volume and desorption conditions, were studied and optimized. Under the optimal MSPE conditions, the extraction percentage of CPZ was 74%, 27% and 16% in water, urine and plasma samples, respectively. The limits of detection （LODs） of the proposed approach were 0.1, 5.0 and 10ng/mL in water, urine and plasma samples, respectively. The relative standard deviations （RSDs） based on five replicate determinations at 10 ng/mL level of CPZ was 1.2%. Good linear behaviors over the investigated concentration ranges （0.25-300 ng/mL） with good coefficient of determination, R2 〉 0.9998, were obtained. Good spike recoveries with relative errors less than 9.0% were obtained when applying the proposed method to water, urine and plasma samples.

Changes in Tissue Metals After Cadmium Intoxication and Intervention With Chlorpromazine in Male Rats

Cadmium (Cd), one of the most dangerous heavy metals, has a very similar ionic radius to calcium (Ca). The interference of cadmium in calcium homeostasis may play an important role in cadmium toxicity. Recent reports indicate that calmodulin (CaM) inhibitors such as trifluoperazine and chlorpromazine (CPZ) could protect rodents against cadmium toxicity. It was also reported that pretreatment of mice with zinc (Zn) could reduce the adverse effects induced by cadmium. The aim of this study is to determine whether Cd changes the balance of other essential metals such as Zn and copper (Cu) in rat tissues, and whether CPZ can reverse these changes which are induced by cadmium intoxication. Adult male Sprague Dawley (SD) rats were injected intraperitoneally (ip) with cadmium chloride (CdCl 2) (0.2, 0.4, 0.8 mg Cd/kg body weight) alone and 0.4mg Cd/kg in association with CPZ (5 mg/kg) daily for a week. The control animals were injected with normal saline only. The results showed that the cadmium content in the liver, kidney and testis increased significantly with a dose response relationship. Cadmium treatment markedly increased the Zn and Ca content in some of the tissues. Hepatic and renal metallothionein (MT) increased significantly after cadmium intoxication. CPZ treatment, however, reduced cadmium content in liver, but not blood and kidney. CPZ seemed to decrease the content of MT in liver and significantly increase the amounts of MT in kidney. These data suggest that the intervention of cadmium with tissue essential metals may play a role in cadmium toxicity in rats, and calmodulin inhibitors to some extent can reduce the adverse effect of cadmium by decreasing the cadmium load in tissues and reversing the unbalance of essential metals.

Dispersive Liquid-liquid Microextraction Combined with High-performance Liquid Chromatography for the Determination of Clozapine and Chlorpromazine in Urine

A simple method has been proposed for the determination of clozapine （CLZ） and chlorpromazine （CPZ） in human urine by dispersive liquid-liquid microextraction （DLLME） in combination with high-performance liquid chromatography-ultraviolet detector （HPLC-UV）. All important variables influencing the extraction efficiency, such as pH, types of the extraction solvent and the disperser solvent and their volume, ionic strength and centrifugation time were investigated and optimized. Under the optimal conditions, the limit of detection （LODs） and quantification （LOQs） of the method were 13 and 39 ng/mL for CLZ, and 2 and 6 ng/mL for CPZ, respectively. The relative standard deviations （RSDs） of the targets were less than 5.1% （C=0.100 μg/mL, n=9）. Good linear behaviors over the tested concentration ranges were obtained with the values of R20.999 for the targets. The absolute extraction efficiencies of CLZ and CPZ from the spiked blank urine samples were 98.3% and 97.8%, respectively. The applicability of the technique was validated by analyzing urine samples and the mean recoveries for spiked urine samples ranged from 93.3% to 105.0%. The method was successfully applied for the determination of CLZ and CPZ in real human urine.

Study on New Spectrophotometric Determination of Arsenic (V) with Chlorpromazine

It was shown that a new sensitive spectrophotometric method for the determination oftrace arsenic with chlorpromazine by the formation of heteropoly arsenomolybdic chlorpromazinecomplex in aqueous phase.

The inhibition effect of Chlorpromazine against the β-lactam resistance of MRSA

Objective:To investigate the gene related to β-lactam resistance and to confirm the mechanism about a synergy effect between CPZ and β-lactam antibiotics.Methods:To measure antibacterial activity,we performed a minimum inhibitory concentration(MIC) and synergy test.Transmission electron microscopy(TEM) was used in morphological analysis.To analyze gene expression,we conducted reverse transcriptase polymerase chain reaction(PCR).Results:We confirmed a synergy effect between CPZ and β-lactam antibiotics.Furthermore,we observed that CPZ affect the cell envelope of MRS A by using TEM.At the gene level,CPZ reduced the expression of resistance genes.Conclusions:Through this result,we hypothesize that a decrease of resistance factor expressions was caused by CPZ because it disrupts the activity of a sensor protein located in the cell membrane.

Activity of chlorpromazine on nfa1 and Mp2CL5 genes of Naegleria fowleri trophozoites

Amoeba treatment of patients suffering from pri-mary amoebic meningoencephalitis caused by Naegleria fowleri has not been successful. Dam-aged morphology and effect on genes of N. fowleri as the result of its initial interaction with drug may provide clue to the success of treatment. In this study, we investigated the activity of chlorpromazine compared with amphotericin B and voriconazole against N.fowleri Khon Kaen strain using cell based assay and molecular techniques. Scanning electron and light micro-graph showed the drug interaction of treated amoebae with 0.098 ug/ml chlorpromazine was faster than 0.002 ug/ml amphotericin B and 12.5 ug/ml of voriconazole. The morphological cha-racteristics of treated amoebae with Gomori’s trichrome stain correlated to the scanning elec-tron microscope study. The effect of drugs to nfa1 and Mp2CL5 genes of treated amoebae found that at 120 min post exposure, chlorpromazine, voriconazole inhibited both genes except amphotericin B. Most of drug inhibited nfa1 except fluconazole. The results evaluated that chlorpromazine was higher potency and rapidly activity than amphotericin B and voriconazole against N. fowleri trophozoites.

Oxidation of Amino Acids by Chlorpromazine Cation Radical and Co-Catalysis by Chlorpromazine

The long-tem use of chlorpromazine (CPZ) may cause severe side effects. This property of CPZ might be related to pro-oxidant effects of the chlorpromazine cation radical (CPZ·+), which can be easily generated by catalytic action of peroxidases, including the neutrophil myeloperoxidase (MPO) and by methemoglobin. Aiming the comprehension of a putative physiological effect of CPZ·+ upon biomolecules, in this work we studied the reactivity of CPZ·+ with amino acids and the co-catalytic effect of CPZ during the oxidation of amino acids by horseradish peroxidase (HRP)/H2O2 system. We also studied whether natural blood plasma components as ascorbic acid, uric acid and nitrite could inhibit the oxidative effect of CPZ·+. We found that tryptophan, tyrosine and cysteine were easily oxidized by pure CPZ·+. Other amino acids as methionine, glycine, phenylalanine, aspartic acid and lysine were unreactive. The decomposition of CPZ·+ was exacerbated by uric acid, ascorbic acid and nitrite, provoking inhibition in the amino acids oxidation. In experiments with HRP/H2O2, and using CPZ as a co-catalyst, a strong effect upon oxidation of tryptophan, tyrosine and cysteine was obtained. It was also found that tryptophan was more reactive than tyrosine with CPZ·+, a feature that could be related to the recently described favorable interaction between tryptophan and CPZ. The use of CPZ as a co-catalyst is discussed regarding its role in the efficient oxidation of tryptophan.

STUDY ON SPECTROPHOTOMETRIC DETERMINATION OF CHLORPROMAZINE

The method is based on the oxidation of chlorpromazine with ammonium metavanadate in pH 2.4 solution, the absorbance of coloured compound was measured at 530 nm. Calibration graphs are linear over the concentration range 0 to approximately 250 mu g/mL. The apparent molar absorptivity was 1.28 multiplied by 10**3 L center dot mol** minus **1 center dot cm** minus **1. The proposed method was applied to the determination of chlorpromazine tablets with satisfactory results. (Author abstract) 4 Refs.

Determination of chlorpromazine in porcine muscle using high performance liquid chromatography-tandem mass spectrometry

A rapid and accurate high performance liquid chromatography tandem mass spectrometry（HPLS-MS） method was established for quantification of chlorpromazine in pork. The porcine samples were pretreated with acetonitrile to precipitate proteins and followed by extraction with tert--butyl methyl ether（TBME）. The separation was performed on a 5 μm Agilent XDB--C18 column with gradient elution. The mobile phase A was 0.01 mol/L ammonium formate in water and mobile phase B was acetonitrile. The flow rate was at 0.8 mL/min. Quantification was performed on a triple-quadrupole tandem mass spectrometer using the multiple selected reaction monitoring（MRM） mode. Transition of m/z ＋319.1 to 58.1 was used for the quantification of chlorpromazine. The method was validated at the concentration range of 0.4040 μg/kg to 8.080 μg/kg for chlorpromazine with correlation coefficient of 0.9999. The spiked recoveries were more than 80.0% and the limit of detection（LOD） was 0.052 μg/kg. The developed method, which offers advantages of convenience, rapid, specificity and higher sensitivity, can be used for determination of chlorpromazine hydrochloride in porcine muscles.

Chlorpromazine protects against acetaminophen-induced liver injury in mice by modulating autophagy and c-Jun N-terminal kinase activation

Background and aim:Overdose of acetaminophen(APAP)leads to liver injury,which is one of the most common causes of liver failure in the United States.We previously demonstrated that pharmacological activation of autophagy protects against APAP-induced liver injury in mice via removal of damaged mitochondria and APAP-adducts(APAP-ADs).Using an image-based high-throughput screening for autophagy modulators,we recently identified that chlorpromazine(CPZ),a dopamine inhibitor used for anti-schizophrenia,is a potent autophagy inducer in vitro.Therefore,the aim of the present study is to determine whether CPZ may protect against APAP-induced liver injury via inducing autophagy.Methods:Wild type C57BL/6J mice were injected with APAP to induce liver injury.CPZ was administrated either at the same time with APAP(co-treatment)or 2 h later after APAP administration(post-treat-ment).Hemotoxyline and eosin(H&E)staining of liver histology,terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling(TUNEL)staining of necrotic cell death as well as serum levels of alanine aminotransferase(ALT)were used to monitor liver injury.Results:We found that CPZ markedly protected against APAP-induced liver injury as demonstrated by decreased serum levels of ALT,liver necrotic areas as well as TUNEL-positive cells in mice that were either co-treated or post-treated with CPZ.Mechanistically,we observed that CPZ increased the number of autolysosomes and decreased APAP-induced c-Jun N-terminal kinase activation without affecting the metabolic activation of APAP.Pharmacological inhibition of autophagy by chloroquine partially weak-ened the protective effects of CPZ against APAP-induced liver injury.Conclusions:Our results indicate that CPZ ameliorates APAP-induced liver injury partially via activating hepatic autophagy and inhibiting JNK activation.

Study on the interaction between palladium(II)-chlorpromazine hydrochloride and sodium tungstate by the resonance Rayleigh scattering, second-order scattering and frequency doubling scattering spectra and its analytical application

The interaction between palladium(II)-chlorpromazine hydrochloride and sodium tungstate was investigated by ultravioletvisible absorption,resonance Rayleigh scattering(RRS),second-order scattering(SOS)and frequency doubling scattering (FDS)spectroscopy.In pH 5.3 Britton-Robinson(BR)buffer medium,chlorpromazine hydrochloride(CPZ)reacted with Pd(II) to form 2:1 cationic chelate,which further reacted with Na2WO4 to form a 1:1 ternary ion-association complex ([Pd(CPZ)2]·WO4).As a result,the signal intensities of RRS,SOS and FDS were enhanced greatly,and the enhancements of scattering were proportional to the CPZ concentration in a certain range.Their maximum wavelengths were located at 310 nm, 570 nm and 391 nm,respectively and the detection limits(3)were 1.6 ng/mL(RRS method),3.2 ng/mL(SOS method)and 5.6 ng/mL(FDS method).The optimum reaction conditions,the influences of coexisting substances and analytical application were mainly investigated by RRS method due to its highest sensitivity.A highly sensitive,simple,rapid and new method had been proposed to determine CPZ in the pharmaceutical form and residue of CPZ in pork.In addition,the Gibbs free energy change(△Gf)of ion-association reaction was computed by using B3LYP/3-21g*/LanL2dz method.The formation of ion-association and the reasons for the enhancement of RRS were also discussed.

Study on the interactions of chlorpromazine hydrochloride and promethazine hydrochloride with nucleic acids by resonance Rayleigh scattering spectrum

The interactions of phenothiazine such as chlorpromazine hydrochloride(CPZ·HCl)and promethazine hydrochloride(PZ·HCl),with nucleic acids(NA)have been investigated.The CPZ-NA system can produce very intense resonance Rayleigh scattering(RRS),but the RRS intensity of the PZ-NA system is very weak.The energy relationship of the two reaction systems has been calculated by the AM1 and B3LYP of density functional methods for quantum chemistry,the binding site and interacting model of CPZ-NA and PZ-NA are studied.The results show that CPZ has strong binding ability with nucleic acids,but PZ hardly react with nucleic acids.It can be expected that RRS method may be a useful means for molecular recognition of nucleic acids and the molecular design of gene medicine in the future.Moreover,the method is used for the quan-titative determination of nucleic acids by employing chlorpromazine hydrochloride as reagent,which has very high sensitivity and good selectivity.Therefore,a sensitive,simple and rapid new method has been developed for the determination of nucleic acids.

LC-MS/MS同位素稀释法测定食品中地西泮和氯丙嗪残留量

This article concentrates on the method of the determination of diazepam and chlorpromazine residue in meat and kidney,by using HPLC-MS/MS.The D6-chlorpromazine was added to sample as an internal standard.Then extracted the sample with acetonitrile,cleaned up the extract through Oasis HLB cartridge.Determination and confirmation is made by means of liquid chromatography-tandem mass spectrometry,using internal standard method.The limit of quantitation of chlorpromazine and diazepam are all 1.0 μg/kg.

History of the dopamine hypothesis of antipsychotic action

The dopamine hypothesis of how antipsychotic drugs exert their beneficial effect in psychotic illness has an interesting history that dates back to 1950.This hypothesis is not to be confused with the dopamine hypothesis of schizophrenia;the aim of the latter is to explain the etiology of schizophrenia.The present review does not deal with schizophrenia but,rather,with the historical development of our current understanding of the dopamine-associated actions of the drugs that reduce the symptoms of psychosis.This historical review begins with the serendipitous discovery of chlorpromazine,a drug synthesized around a chemical core that initially served to produce man-made dyes.This molecular core subsequently contributed to the chemistry of antihistamines.It was with the aim of producing a superior antihistamine that chlorpromazine was synthesized;instead,it revolutionized the treatment of psychosis.The first hypothesis of how this drug worked was that it induced hypothermia,a cooling of the body that led to a tranquilization of the mind.The new,at the time,discoveries of the presence of chemical transmitters in the brain soon steered investigations away from a temperature-related hypothesis toward questioning how this drug,and other drugs with similar properties and effects,modulated endogenous neurotransmission.As a result,over the years,researchers from around the world have begun to progressively learn what antipsychotic drugs do in the brain.

The Therapeutic Effects of Ling Gui Zhu Gan Tang Mixture in 50 Psychotic Patients with Obesity Induced by the Psychoactive Drugs

In order to observe the therapeutic effects of Ling Gui Zhu Gan Tang Mixture (芩桂术甘汤) on obesity induced by psychoactive drugs, 100 psychotics with obesity induced by psychoactive drugs were randomly divided into a treatment group (50 cases)and a control group (50 cases) for a 8-week treatment.The changes were determined by means of the Brief Psychiatric Rating Scale (BPRS) and the Treatment Emergent Symptom Scale (TESS) with the body weight recorded before and after treatment. The results showed that the total effective rate was 72% in the treatment group, and 14% in the control group,with the former obviously superior to the latter (P＜0.01). The BPRS scores were 33.02t7.34 in the treatment group and 32.39± 3.51 in the control group before treatment; and 20.38±5.10 in the treatment group and 20.82± 1.75 in the control group after treatment. The BPRS scores were obviously reduced after treatment in the two groups (both P＜0.01), but with no significant difference between the two groups (P＞0.05). This indicates that the Ling Gui Zhu Gan Tang Mixture does not influence the curative effect of the psychoactive drugs while showing the body weight-reducing effect. Therefore, the Ling Gui Zhu Gan Tang Mixture can be used for those psychotic patients with obesity induced by the psychoactive drugs (the incidence is 10-25%) in their continuous course of treatment with the latter drugs.

Twenty-five Cases of Obstinate Hiccup Treated by Point Injection at Tianding

From 1997 to 2000, the author treated 25 cases of obstinate hiccup by injecting chlorpromazine and 654-2 injection at Tianding (LI 17), with satisfactory therapeutic results as reported in the following.

Inhibitory Effect of 5-Adenylic Acid on Bitter Taste of Antipsychotic Drugs

The purpose of the present study was to examine the effect of adenylic acid (adenosine 5-monophosphate;AMP), a known nutritional enhancer, on inhibiting the bitterness of antipsychotic medicines administered to patients with mental illnesses, including children. First, we chose four antipsychotic medicines, amitriptyline hydrochloride (AMT), chlorpromazine hydrochloride (CPZ), haloperidol (HPD) and risperidone (RIS) and evaluated the inhibition of their bitterness by AMP through taste sensor measurements. AMP showed a significant bitterness inhibition effect on all drugs. Second, MarvinSketch analysis revealed the potential formation of electrostatic interactions between ionic forms (IV) of AMP and ionic (cationic) forms of each drug, which resulted in bitterness suppression. Third, chemical shift perturbations in 1H-NMR studies suggested an interaction between the phosphate group of AMP and amino group of AMT, CPZ, HPD and RIS. Last, conventional elution experiments of up to 1 min simulating oral cavity conditions were performed for 1 whole AMT tablet, half AMT tablet, crushed half AMT tablet, and crushed AMT tablet containing AMP powder/solution (1, 3 mM potency). The taste sensor output values of the crushed AMT tablet containing AMP powder/solution (1, 3 mM potency) were significantly lower than those of the crushed tablet.

Interaction of antipsychotic drug with novel surfactants: Micellization and binding studies

The interaction of cationic gemini surfactants(alkanediyl-α,ω-bis(alkyl dimethylammonium bromide)) with an antipsychotic drug(chlorpromazine hydrochloride(CPZ)) has been investigated. Various micellar and interfacial parameters have been deliberated by surface tension measurement to report the nature of interactions between drug and novel surfactant mixtures. The behavior of mixed systems, their compositions and activities of components have been analyzed in the light of Rubingh's theory. The results indicate synergism in the binary mixtures.The binding study between CPZ and surfactants has been done by spectroscopic techniques such as UV–visible and fluorescence. The results are discussed in the light of the use of gemini surfactants as promising drug delivery agents for phenothiazine drugs, and hence, improve their bioavailability.