Liquid chromatographic–mass spectrometric determination of haloperidol and its metabolites in human plasma and urine

Arinobu, Tetsuya; Hattori, Hideki; Iwai, Masae; Ishii, Akira; Kumazawa, Takeshi; Сузукі, Осаму; Seno, Hiroshi

doi:10.1016/s1570-0232(02)00175-7

Cited by 48 publications

(38 citation statements)

References 24 publications

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“…However, previous studies [14,20] using LC-MS exhibited rather higher detection limits of CPHP (75~300 ng/mL). Assumed that the LOQ of this study (1 ng/ mL) was much lower than the previous reports, the current method might be more appropriate to analyze CPHP in human biological samples.…”

Section: Discussionmentioning

confidence: 88%

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Development and validation of a HPLC-UV method for 4-(4-chlorophenyl)-4-hydroxypiperidine (CPHP), a toxic metabolite of haloperidol, in humans: providing in vivo evidence of CYP3A4-mediated CPHP formation

Park

Shin

2016

Transl Clin Pharmacol

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We developed a high-performance liquid chromatographic procedure for the determination of 4-(4-chlorophenyl)-4-hydroxypiperidine (CPHP), a toxic metabolite of haloperidol, in human. Chromatographic analysis was performed on a reverse-phase C 18 column with a mobile phase containing 50 mM potassium phosphate buffer/acetonitrile (75:25, vol/vol) using UV detection with a wavelength of 220 nm. The limits of detection for CPHP were 1 ng/ml in urine and the assay was linear over the concentration range of 2-500 ng/ml for urine. This analytical method was applied to measure CPHP in human. Nineteen healthy subjects were enrolled and all subjects received a single oral dose of 5 mg haloperidol following a treatment of placebo or itraconazole at 200 mg/day for 10 days in a randomized crossover manner. CPHP was detected in urine samples and average recovered amount of CPHP was 81.31 μg/24 hr in the placebo phase and it was significantly reduced to 30.34 μg/24 hr after itraconazole treatment. The finding provides in vivo evidence that CPHP is an in vivo metabolite of haloperidol in human and its formation is mediated by CYP3A4.

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Section: Discussionmentioning

confidence: 88%

“…[14,15] However, these methods showed a poor sensitivity. Fang et al developed an assay method of CPHP using GC in biological samples of rats and revealed that CPHP was a major metabolite of haloperidol in rats.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a HPLC-UV method for 4-(4-chlorophenyl)-4-hydroxypiperidine (CPHP), a toxic metabolite of haloperidol, in humans: providing in vivo evidence of CYP3A4-mediated CPHP formation

Park

Shin

2016

Transl Clin Pharmacol

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“…The results show that the best sensitivity and linear range is attained at 3.0 wt% of the ion-pair for electrode P and 1.0 % for electrode g as shown in (Table 1, electrode #5) and (Table 2, electrode #6). Further addition of the ion-pair resulted in a little decrease in the response of the electrodes that is most probably due to some inhomogenieties and possible saturation of the membrane as given in Table 2, electrode #10 and 11 (32).…”

Section: Effect Of Ion-pairmentioning

confidence: 99%

“…Therefore, the determination of trace amounts of HP ion in biological fluids is necessary. Several analytical methods have been reported for the assay of haloperidol including capillary electrophoresis (17), acidimetric titration in non-aqueous medium (18), uV spectrophotometry (19)(20)(21), derivative spectrophotometry (22), colorimetry (23), H-nuclear magnetic resonance spectroscopy (24), densitometry (25), gas chromatography (gC) with electron-capture detection (26) gC with surface ionization detection (27), liquid chromatography (lC) with electrochemical detection (28), lC with uV detection (29), gas-lC with nitrogen-phosphorus detection (30,31), lC with mass spectrometric (MS) detection (32,33), high-performance liquid chromatography (HPlC) with diode array detection (34), HPlC with uV-VIS detection (35,36), micellar electrokinetic chromatography (37), voltammetry (38) and potentiometry (3). These methods are highly sensitive.…”

Section: Introductionmentioning

confidence: 99%

Determination of haloperidol drug in ampoules and in urine samples using a potentiometric PVC-membrane and graphite coated wire electrodes

Shawish¹,

Tamous²,

Shaheen³

et al. 2016

Marmara Pharmaceutical Journal

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“…A literature search has shown several analytical methods for analysis of antipsychotic drugs, including haloperidol, in biological fluids (2,3), spectrophotometric methods for the determination of haloperidol (4), an adsorptive stripping voltammetry assay for determination of haloperidol in bulk form (5), an HPLC method for determination of haloperidol and its metabolites in plasma (6). Although some RP HPLC methods have been developed for the degradation study of haloperidol (7,8), there are no references in the literature concerning chemometrics approach to the development and validation of the RR RP-HPLC method for simultaneous determination of haloperidol and related compounds specified as impurities.…”

mentioning

confidence: 99%

Use of chemometrics for development and validation of an RP-HPLC method for simultaneous determination of haloperidol and related compounds

Petkovska¹,

Dimitrovska²

2008

Acta Pharmaceutica

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Haloperidol is one of the most widely used antipsychotic drugs in the treatment of schizophrenia, mania and other psychiatric disorders (1). Chemically, haloperidol (Hal) is 4-[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]-1-(4-fluorophenyl)-1-butanone. The drug has six known related compounds specified as impurities: 4-(4-chlorophenyl)-4-hydroxy A rapid resolution reversed-phase high performance liquid chromatographic (RR RP-HPLC) method has been developed and validated for simultaneous determination of haloperidol and six related compounds. Investigated matrix was a laboratory mixture of a therapeutic active substance haloperidol and its six related compounds in concentration ratio 300:1. Experimental design was used during method optimization (full factorial 2 3 design) and robustness testing (Central Composite Circumscribed design). Three factors: organic phase variation during gradient elution, flow rate and gradient rise time were independent variables. To estimate the system response during the optimization procedure and robustness testing, resolution (R s ) and a chromatographic response function (CRF) were used. Chromatography was performed with the mobile phase containing phosphate buffer pH 6.5 and acetonitrile as organic modifier. Separation was achieved using gradient elution (organic phase fraction changed linearly from 20 to 72 %) over 7 min. A Zorbax Eclipse XDB C18 Rapid Resolution HT 4.6 mm´50 mm, 1.8 mm particle size, column was used at 25°C at a flow rate of 1.5 mL min -1 . UV detection was performed at 230 nm. The total time for chromatographic separation was 5.5 min with a total analysis time of 7.0 min. The method was validated for its linearity, precision, modal recovery and robustness.

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Liquid chromatographic–mass spectrometric determination of haloperidol and its metabolites in human plasma and urine

Cited by 48 publications

References 24 publications

Development and validation of a HPLC-UV method for 4-(4-chlorophenyl)-4-hydroxypiperidine (CPHP), a toxic metabolite of haloperidol, in humans: providing in vivo evidence of CYP3A4-mediated CPHP formation

Development and validation of a HPLC-UV method for 4-(4-chlorophenyl)-4-hydroxypiperidine (CPHP), a toxic metabolite of haloperidol, in humans: providing in vivo evidence of CYP3A4-mediated CPHP formation

Determination of haloperidol drug in ampoules and in urine samples using a potentiometric PVC-membrane and graphite coated wire electrodes

Use of chemometrics for development and validation of an RP-HPLC method for simultaneous determination of haloperidol and related compounds

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