Determination of chlorpromazine in the blood and brain of mice by high performance liquid chromatography combined with electrochemical detection.

Shibanoki, Shinji; Gotoh, Yukinobu; Ito, Koichi

doi:10.1254/jjp.35.169

Cited by 10 publications

(8 citation statements)

References 15 publications

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“…Although extrapolation of this data to man will obviously require further studies, it should be noted that the plasma levels of CPZ in rats and mice treated with doses of CPZ that inhibit TNF production in this study are well in the range (50-600 ng/ml) observed in patients treated with pharmacologically effective doses of CPZ (23)(24)(25) .…”

Section: Resultsmentioning

confidence: 58%

Protective effect of chlorpromazine on endotoxin toxicity and TNF production in glucocorticoid-sensitive and glucocorticoid-resistant models of endotoxic shock.

Gadina

Bertini

Mengozzi

et al. 1991

The Journal of Experimental Medicine

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SummaryThe present study was designed to define the potential ofchlorpromazine (CPZ) as a protective agent against lipopolysaccharide (LPS) toxicity in comparison with glucocorticoids, and to obtain initial correlations with its effects on the levels of tumor necrosis factor (TNF), a pivotal mediator of endotoxic shock. It was found that CPZ protects mice, normal or adrenalectomized, and guinea pigs against lethality of LPS, and inhibited TNF serum levels, like dexamethasone (DEX), a well-known inhibitor ofTNF synthesis. CPZ protected against LPS lethality when administered 30 minutes (min) before, simultaneously, or up to 10 min after LPS and was ineffective when given 30 min after LPS, paralleling the inhibitory effect on TNF production . In another experimental model, where mice were sensitized to LPS toxicity by actinomycin D, CPZ significantly inhibited LPS lethality and hepatotoxicity, whereas under these conditions DEX was inactive. These experiments indicate that CPZ has a protective action in both glucocorticoid-sensitive and -resistant models of endotoxic shock. T umor necrosis factor (TNF) is a key mediator in the toxic effect ofendotw in (LPS) and in the pathogenesis of septic shock . In fact, serum levels of TNF are high after LPS administered to animals and human volunteers, or in septic patients (1, 2), while administration of antiTNF antibodies protects against the lethal effect of LPS and live bacteria in a variety of animal models (3, 4).AntiTNF antibodies are also protective in a variety of animal models of human diseases, including cerebral malaria (5), bacterial meningitis (6), bleomycin lung toxicity (7), liver ischemia/reperfusion damage (8), and graft-versus-host reaction (9), indicating an involvement ofTNF in the pathogenesis of these diseases . Therefore, TNF might be an important target for pharmacological action, and inhibitors of its synthesis might be useful in the therapy of these diseases . The well-known inhibitory effect ofglucocorticoids on TNF synthesis is thought to be connected with protective action of glucocorticoids in endotoxic shock (10)(11)(12).Previous data from this laboratory have shown that chlorpromazine (CPZ)t protects mice against the lethal effect of LPS and IL1, but not ofTNF (13). The objective ofthe present study was to define the potential of CPZ to block LPS toxicity in comparison with glucocorticoids and to obtain ini-1 Abbreviations used in this paper. Act D, actinomycin D : CPZ, chlorpromazine; DEX, dexamethasone; GPT, glutamate pyruvate transaminase . 1305tial correlations with its effect on the levels of TNF. For this purpose, we have studied the effect of CPZ on LPS toxicity and induction of TNF in various experimental models, including : (a) high-dose LPS (30 mg/kg) in mice, (b) administration of LPS (5 mg/kg) in guinea pigs, which are more sensitive to LPS than mice in terms of lethality and TNF induction (14), (c) adrenalectomized mice, known to be more sensitive to LPS toxicity and TNF induction (11,15), and (d) mice pretreated with actinomycin ...

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Section: Resultsmentioning

confidence: 58%

Protective effect of chlorpromazine on endotoxin toxicity and TNF production in glucocorticoid-sensitive and glucocorticoid-resistant models of endotoxic shock.

Gadina

Bertini

Mengozzi

et al. 1991

The Journal of Experimental Medicine

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“…Suitable extraction solvents, such as ethyl acetate (Baldessarini et al, 1993;Castel-Branco et al, 2003;Greig et al, 1988;Md et al, 2014;Milane et al, 2009;Minocha et al, 2012;Oberoi et al, 2013;Perin et al, 2017;Wang et al, 2011;Xia et al, 2004), ethers like diisopropyl ether (Yang et al, 2015;Zhang et al, 2007bZhang et al, , 2007c, diethyl ether (Jiang et al, 2008;Shimokawa et al, 2005) and methyl tert-butyl ether (Li et al, 2013;Turnpenny & Fraier, 2009), chlorinated solvents like chloroform (Nakashima et al, 2002;Nakashima et al, 2003;Somani & Khalique, 1985) and methylene dichloride (Aravagiri et al, 1998;Aravagiri et al, 1999), hexane (Tsuneizumi et al, 1992) and isopropyl alcohol (Yasir et al, 2017) and solvent combinations such as diisopropyl ether-methyl chloride (Zhang et al, 2008), ethyl acetate-diisopropyl ether (El Zahar et al, 2018, heptane-isoamyl alcohol (Shibanoki et al, 1984) and benzene-isoamyl alcohol (Lister et al, 1983), have all been successfully applied to various analytes. The method often involves a pH adjustment to improve transfer of analytes into the organic phase.…”

Section: Liquid-liquid Extractionmentioning

confidence: 99%

“…The most common methods utilize C 18 reversed phase (RP) columns with varying ratios of mobile phases, as shown in Table 1. The columns used are: Waters Atlantis (El Yang et al, 2015;Zhang et al, 2007bZhang et al, , 2007c, Ultrasphere (Shibanoki et al, 1984), Agilent Eclipse Plus (Liang et al, 2012), Hypersil (Couet et al, 1990;Jiang et al, 2008;Nicot et al, 1986;Weigmann et al, 1999), μBondpack (Colovic et al, 2004;Lister et al, 1983;Somani & Khalique, 1985), Phenomenex Kinetex (Dalvi et al, 2018), Develosil (Nakashima et al, 2002;Nakashima et al, 2003), Xbridge (Nirogi et al, 2013), XTerra ® MS (Ligneau et al, 2007;Minocha et al, 2012), Cosomil (Yasir et al, 2017), LiChrospher (Castel-Branco et al, 2003Respaud et al, 2012), Intersil ODS-2 (Ohmori et al, 2000), Wakopak Handy ODS (Tomita et al, 2007), LiChroCART (Fortuna et al, 2013;Haque et al, 2012;Singh et al, 2011), Zorbax Eclipse (Oberoi et al, 2013;Roma nski et al, 2014;Wang et al, 2011), Gemini (Perin et al, 2017;Zheng et al, 2015), Radial-PAK (Workman et al, 1984), Partosil 10 (Greig et al, 1988Sweeney et al, 1985), Luna (Guo et al, 2007;Saigusa et al, 2011), Agilent SB …”

Section: Hplc Techniquesmentioning

confidence: 99%

“…Other fluorometric assays allow for the analysis of melphalan after its derivatization with o-phthalaldehyde (Sweeney et al, 1985), the determination of MDMA with its metabolite MDA and the determination of a mixture of phentermine, fenfluramine and its metabolite norfenfluramine after being subjected to derivatization with 4-(4,5-diphenyl-1H-imidazol-2-yl) benzoyl chloride (Kaddoumi et al, 2003;Tomita et al, 2007). Electrochemical detection is another method that has been used for studying drug distribution between blood and brain to assist with the determination of the effects of chlorpromazine, olanzapine, a mixture of risperidone and its metabolite 9-hydroxy-risperidone and a mixture of the neuroleptics, haloperidol, bromperidol, fluphenazine, promazine, chlorpromazine with its metabolites nor-l-and nor-2-chlorpromazine, and thioridazine with its metabolites mesoridazine, sulforidazine and northioridazine (Aravagiri et al, 1998;Aravagiri et al, 1999;Shibanoki et al, 1984;Tsuneizumi et al, 1992). Linear ranges and sensitivity including limit of detection, limit of quantification and/or lower limit of quantification for the different HPLC detection methods are illustrated in Table 1.…”

Section: Hplc Techniquesmentioning

confidence: 99%

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Assessment of brain‐to‐blood drug distribution using liquid chromatography

Zahar

Sutton

Bartlett

2021

Biomedical Chromatography

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Delivery of already existing and new drugs under development to the brain necessitates passage across the blood-brain barrier (BBB) with its tight intercellular junctions, molecular components and transporter systems. Consequently, it is critical to identify the extent of brain permeation and the partitioning across the BBB. The interpretation of brain-to-blood ratios is considered to be a significant and fundamental approach for estimating drug penetration through BBB, the brain-targeting ability and central nervous system (CNS) pharmacokinetics. Among the different bioanalytical techniques, liquid chromatography with various detectors has been widely used for determination of these ratios. This review defines the different approaches for sample preparation, extraction techniques and liquid chromatography procedures concerned with the determination of drugs in blood and brain tissues and the assessment of brain-to-blood levels. These approaches are expanded to cover the analysis of several drug classes such as CNS-acting drugs, chemotherapeutics, antidiabetics, herbal medicinal products, radiopharmaceuticals, antibiotics and antivirals. Accordingly, stability in biological matrices and matrix effects are investigated.The different administration/formulation effects and the possible deviations in these ratios are also disscussed.

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“…High performance liquid chromatography (HPLC) is becoming regarded as a more useful method for the determination of the phenothiazines ) and has been used to quantify CPZ and THD in human plasma from patients receiving neuroleptic medication (Cooper et al 1983;Skinner et al 1981;Stoll et al 1984). However, little research has focused on levels of these drugs in either brain tissue from animals receiving neuroleptics (Shibanoki et al 1984;Kilts et al 1984) or human postmortem brain tissue from patients receiving drug therapy (Dinovo et al 1978). We have therefore developed a method which allows levels of CPZ, THD and some of their metabolites to be measured simultaneously in postmortem brain tissue using HPLC with coulometric electrochemical detection (HPLC-EC).…”

mentioning

confidence: 99%

HPLC with electrochemical detection to measure chlorpromazine, thioridazine and metabolites in human brain

Svendsen

Bird

1986

Psychopharmacology

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Thirteen phenothiazine compounds were separated chromatographically using high performance liquid chromatography with coulometric electrochemical detection. These could be extracted from brain tissue using direct homogenization in tetrahydrofuran followed by one centrifugation, evaporation of supernatant and reconstitution in water. Fluphenazine was used as the internal standard. The absolute lower limit of detection was approximately 50 pg/mg wet tissue, and recovery rates for most standards added to brain homogenates were greater than 85%. Chromatograms from patients receiving chlorpromazine (600 mg) and thioridazine (600 mg) are shown and endogenous brain levels quantified. The results are discussed with respect to their relevance in schizophrenic research.

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Determination of chlorpromazine in the blood and brain of mice by high performance liquid chromatography combined with electrochemical detection.

Cited by 10 publications

References 15 publications

Protective effect of chlorpromazine on endotoxin toxicity and TNF production in glucocorticoid-sensitive and glucocorticoid-resistant models of endotoxic shock.

Protective effect of chlorpromazine on endotoxin toxicity and TNF production in glucocorticoid-sensitive and glucocorticoid-resistant models of endotoxic shock.

Assessment of brain‐to‐blood drug distribution using liquid chromatography

HPLC with electrochemical detection to measure chlorpromazine, thioridazine and metabolites in human brain

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