An electrochemical sensor for ifosfamide, acetaminophen, domperidone, and sumatriptan based on self-assembled MXene/MWCNT/chitosan nanocomposite thin film.

New multi-walled carbon nanotubes supported on Ti3C2-MXene and chitosan (chit) composite film-based electrochemical sensor for ifosfamide (IFO), acetaminophen (ACOP), domperidone (DOM), and sumatriptan (SUM) have been developed. Ti3C2-MXene was synthesized by a fluoride method. Structural and chemical characterizations suggested the successful preparation of Ti3C2-MXene with clearly seen layered morphology, defined 0 0 2 diffraction peak at 7.5° and complete absence of 1 0 4 plane at 39°. The electrochemical performance of the sensor was investigated by cyclic voltammetry and adsorptive stripping differential pulse voltammetry. The Ti3C2/MWCNT/Chit modified glassy carbon electrode exhibits enhanced electrocatalytic activities toward the oxidation of target analytes. Excellent conductivity, large surface area, and high catalytic properties of the Ti3C2-MXene showed synergistic effects with MWCNTs and helped in achieving low detection limits of targets with high selectivity and reproducibility. The assay allows determination of IFO, ACOP, DOM, and SUM in the concentration ranges 0.0011-1.0, 0.0042-7.1, 0.0046-7.3, and 0.0033-61 µM with low detection limits of 0.00031, 0.00028, 0.00034, and 0.00042 µM, respectively. The sensor was successfully applied for voltammetric screening of target analytes in urine and blood serum samples with recoveries > 95.21%. Schematic illustration of the synthesis of self-assembled MXene/MWCNT/chitosan nanocomposite is given and its application to the voltammetric determination of ifosfamide, acetaminophen, domperidone, and sumatriptan described. Graphical abstract.

Synthesis of molecular imprinted polymers for selective extraction of domperidone from human serum using high performance liquid chromatography with fluorescence detection.

In this study a novel method is described for selective quantization of domperidone in biological matrices applying molecular imprinted polymers (MIPs) as a sample clean up procedure using high performance liquid chromatography coupled with a fluorescence detector. MIPs were synthesized with chloroform as the porogen, ethylene glycol dimethacrylate as the crosslinker, methacrylic acid as the monomer, and domperidone as the template molecule. The new imprinted polymer was used as a molecular sorbent for separation of domperidone from serum. Molecular recognition properties, binding capacity and selectivity of MIPs were determined. The results demonstrated exceptional affinity for domperidone in biological fluids. The domperidone analytical method using MIPs was verified according to validation parameters, such as selectivity, linearity (5-80ng/mL, r(2)=0.9977), precision and accuracy (10-40ng/mL, intra-day=1.7-5.1%, inter-day=4.5-5.9%, and accuracy 89.07-98.9%).The limit of detection (LOD) and quantization (LOQ) of domperidone was 0.0279 and 0.092ng/mL, respectively. The simplicity and suitable validation parameters makes this a highly valuable selective bioequivalence method for domperidone analysis in human serum.

A case of sudden cardiac death following Domperidone self-medication.

The phenomenon of sudden cardiac death is usually related to the worsening of existing heart conditions leading to ventricular arrhythmia (VA). One of the well-known triggers of SCD is drug-induced prolongation of the QT interval, such as that caused by Domperidone (D). Despite its risk to prolong the QT interval and associated narrow therapeutic index, D is available as an over-the-counter (OTC) drug in many countries such as Italy, Ireland, Netherlands, China, South Africa, Mexico, New Zealand and Chile to treat gastroesophageal reflux and functional dyspepsia. The present paper reports a case of SCD that occurred some hours after D self-administration in a 47-year-old female subject with mitral valve prolapse, thus, predisposed to both VA and SCD. Despite the risks related to D administration, to the best of our knowledge, this particular issue has not been discussed in the medico-legal literature. For this reason, the forensic implications of D administration are discussed focusing on issues related to the self-administration as an OTC drug (as seen in this case), administration to incapacitated subjects, prescription to patients with contraindications and the off-label drug use of D at high and hazardous concentrations to stimulate lactation.

Gold nanoparticles decorated poly-melamine modified glassy carbon sensor for the voltammetric estimation of domperidone in pharmaceuticals and biological fluids.

The electrochemical response of an unmodified glassy carbon (GCE), poly-melamine/GCE and gold nanoparticle (AuNP)/poly-melamine/GCE is compared in the present protocol for the sensitive and selective determination of domperidone (DOM). The AuNPs were synthesized in the laboratory and characterized using UV-visible spectroscopy and Transmission Electron Microscopy (TEM). Melamine was electropolymerized onto the glassy carbon surface using cyclic voltammetry and was investigated using Field Emission Scanning Electron Microscopy (FE-SEM) and Electrochemical Impedance Spectroscopy (EIS). The AuNP/poly-melamine/GCE exhibited the best electrochemical response among the three electrodes for the electro-oxidation of DOM, that was inferred from the EIS, cyclic and square wave voltammetry. The modified sensor showed a sensitive, stable and linear response in the concentration range of 0.05-100µM with a detection limit of 6nM. The selectivity of the proposed sensor was assessed in the presence of high concentration of major interfering molecules as xanthine, hypoxanthine, and uric acid. The analytical application of the sensor for the quantification of DOM in pharmaceutical formulations and biological fluids as urine and serum was also investigated and the results demonstrated a recovery of >95% with R.S.D of <5%.

Effect of silymarin pretreatment on the bioavailability of domperidone in healthy human volunteers.

BACKGROUND: The aim of this study was to investigate the effect of silymarin pretreatment on domperidone oral bioavailability in humans. METHODS: The rats were pretreated with silymarin for 7 days. The transport of domperidone across the rat intestine (duodenum, jejunum, ileum, and colon) was studied by using in vitro everted and non-everted sac methods. Samples were collected at preset time points and replaced with buffer. The drug content in the samples was estimated. The first part of the study included oral administration of 10 mg domperidone tablet alone, and blood was sampled from the antecubital vein. The second part of the study was conducted after a washout period of 2 weeks. Five hundred milligrams of silymarin was administered twice daily for 6 days. On day 7, one tablet each of 10 mg domperidone and 500 mg silymarin were administered concomitantly. RESULTS: In the everted sac and non-everted sac study with silymarin pretreatment, domperidone transport increased from the duodenum, jejunum, ileum, and colon. The silymarin pretreatment increased the bioavailability of domperidone. There was a statistically significant difference in the pharmacokinetic parameters Cmax, T1/2, AUC0-∞, and AUC0-24. CONCLUSIONS: The significant difference in absorption of domperidone on pretreatment with silymarin is due to the inhibition of P-glycoprotein and CYP3A. Silymarin, which inhibits CYP3A4, should be contraindicated for domperidone.

Determination of domperidone in human plasma using high performance liquid chromatography with fluorescence detection for clinical application.

A simple and reliable method for the determination of domperidone in human plasma has been developed. Plasma samples (1mL) were pre-purified by a solid-phase extraction with Bond Elut(®) C18. The separation was achieved with XBridge™ C18 column (150mm×4.6mm i.d., 5µm) at 40°C. The mobile phase was a mixture of acetonitrile and 10mM ammonium acetate buffer (36:64, v/v), adjusted to pH 9.4 with 20% ammonium solution at a flow rate of 1.0mL/min. The peak was detected using fluorescence detector at excitation 282nm and emission 328nm. Retention times for domperidone and internal standard (propranolol) were 8.3min and 11.2min, respectively. The method showed a good linearity (r>0.999), precision (relative standard deviations <10.6%), and extraction recovery (85.7-99.7%) over a concentration of 1-100ng/mL. The lower limit of quantification (LLOQ) was 1.0ng/mL. This proposed method was successfully applied to a pharmacokinetic interaction study of domperidone in healthy Japanese volunteers.

Rapid and sensitive UPLC-MS/MS method for the determination of domperidone in human plasma and its application to pharmacokinetic study.

In this study, a simple, rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method is described for determination of domperidone in human plasma samples using oxcarbazepine as the internal standard (IS). Sample preparation was accomplished through protein precipitation with methanol, and chromatographic separation was performed on an Acquity BEH C18 column (2.1 mm×50 mm, 1.7 µm) with gradient profile at a flow of 0.45 mL/min. Mass spectrometric analysis was performed using a QTrap5500 mass spectrometer coupled with an electro-spray ionization (ESI) source in the positive ion mode. The MRM transition of m/z 426.3→175.2 was used to quantify for domperidone. The linearity of this method was found to be within the concentration range of 0.25-100.0 ng/mL for domperidone in human plasma. Only 1.5 min was needed for an analytical run. The method herein described was superior to previous methods and was successfully applied to the pharmacokinetic study of domperidone in healthy Chinese volunteers after oral administration.

Effect of piperine, a major component of black pepper, on the pharmacokinetics of domperidone in rats.

The present study was aimed to investigate the effect of piperine, a major active ingredient of black pepper, on the pharmacokinetics of domperidone in rats. Animals were given oral (p.o.) or intraperitoneal (i.p.) domperidone (20 mg/kg) alone or together with piperine (20 mg/kg, p.o.). Plasma samples were collected at 0.25, 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0 and 12 hours after drug administration. The concentration of domperidone in the plasma was measured using a HPLC method. The concomitant administration of piperine with oral or intraperitoneal domperidone resulted in a significant (P<0.05) increase in the maximum plasma concentration (Cmax), the mean area under the plasma concentration-time curve (AUC), and the elimination half-life (t1/2) of domperidone as compared to those obtained for domperidone alone. These results suggest that an important pharmacokinetic interaction may occur if piperine is administered concurrently with domperidone.

Identification of domperidone metabolites in plasma and urine of gastroparesis patients with LC-ESI-MS/MS.

Domperidone is a prokinetic agent used to treat gastroparesis. Previous studies reported oxidative metabolites of domperidone, detected by radiometric high-performance liquid chromatography or single quadrupole mass spectrometric techniques. Our aim was to identify domperidone Phase I and Phase II metabolites using liquid chromatography combined with electrospray ionization-enabled tandem mass spectrometry. Domperidone metabolites were identified in the plasma and urine of 11 gastroparesis patients currently being treated with domperidone. In addition, oxidative and conjugative metabolites of domperidone were characterized in human liver subcellular fractions. Seven metabolites were detected in vivo. Domperidone was metabolized to two mono-hydroxylated metabolites (M1 and M2), a de-alkylated metabolite (M5) and a di-hydroxylated metabolite (M7). The mono-hydroxylated metabolites were further glucuronidated to M8, M9 and sulfated to M11. To the best of our knowledge, M7, M8, M9 and M11 have not been reported previously. Five additional metabolites were identified in vitro in human subcellular fractions which comprise two additional mono-hydroxylated metabolites (M3 and M4), an alcohol metabolite (M6) possibly formed from an aldehyde intermediate, and other conjugative metabolites (M10 and M12). M6, M10 and M12 have not been characterized previously. In total, 12 domperidone metabolites including 7 new metabolites were identified in the present study. These results allow a better understanding of domperidone disposition in humans.

Development and validation of UPLC-MS/MS method for determination of domperidone in human plasma and its pharmacokinetic application.

A sensitive, rapid and selective ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method was developed for the determination and pharmacokinetic study of domperidone in human plasma. Diphenhydramine was used as the internal standard. Plasma sample pretreatment involved a one-step liquid-liquid extraction with a mixture of diethyl ether-dichloromethane (3:2, v/v). The analysis was carried out on an Acquity UPLC(TM) BEH C(18) column. The mobile phase consisted of methanol-water containing 10 mmol/L ammonium acetate and 0.5% (v/v) formic acid (60:40, v/v). The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode via electrospray ionizationsource with positive mode. Each plasma sample was chromatographed within 2.1 min. The standard curves for domperidone were linear (r(2) ≥ 0.99) over the concentration range of 0.030-31.5 ng/mL with a lower limit of quantification of 0.030 ng/mL. The intra- and inter-day precision (relative standard deviation) values were not higher than 13% and accuracy (relative error) was from -7.6 to 1.2% at three quality control levels. The method herein described was superior to previous methods and was successfully applied to the pharmacokinetic study of domperidone in healthy Chinese volunteers after oral administration.

Coadministration of domperidone increases plasma levodopa concentration in patients with Parkinson disease.

OBJECTIVES: The aim of this study was to examine the effects of the peripheral dopamine D2-receptor antagonist, domperidone, on the plasma kinetics of levodopa in patients with Parkinson disease (PD). METHODS: In a randomized crossover design, 18 hospitalized patients with PD received a single dose of levodopa/benserazide, 100/25 mg, with or without domperidone, 10 mg, under fasting conditions. Plasma levodopa concentrations were determined up to 3 hours after dose administration. RESULTS: Mean ± SEM levodopa maximum plasma concentration (Cmax) (14.1 ± 2.9 vs 9.7 ± 1.6 µmol/L; P < 0.01), plasma concentration at 30 min (C30 min) (13.7 ± 3.0 vs 8.1 ± 2.0 µmol/L; P < 0.01), and area under the plasma concentration-time curve from 0 to 3 hours (AUC0-3 hr) (15.9 ± 3.1 vs 12.1 ± 2.4 µmol/L · hour; P < 0.05) were significantly higher after coadministration of levodopa with domperidone compared to levodopa alone. Thus, domperidone increased levodopa Cmax and AUC0-3 hr by 1.5- and 1.3-fold, respectively. There were no exacerbations of PD by concomitant domperidone administration. CONCLUSIONS: The results demonstrate that coadministration of domperidone increased the bioavailability of levodopa. This may be the reason for no exacerbation of PD in concomitant administration of domperidone, a dopamine D2-receptor blocker.

Itraconazole and domperidone: a placebo-controlled drug interaction study.

PURPOSE: To determine the influence of itraconazole on the pharmacokinetics, and the CNS and prolactin-elevating effects of domperidone in humans. METHODS: Fifteen healthy volunteers received either itraconazole (200 mg daily) or placebo for 5 days with a double blind, randomized, cross-over design. A single oral 20-mg dose of domperidone was administered to subjects on day 5. Plasma domperidone and serum prolactin concentrations were measured. The effects of domperidone on CNS were also assessed using self-rating scales and electroencephalography. RESULTS: Itraconazole significantly increased domperidone AUC(0-∞) (3.2-fold) and C(max) (2.7-fold) compared with placebo, but had no significant effect on the elimination half-life of domperidone. The CNS effects of domperidone assessed by self-rating of mood and electroencephalography, and the prolactin-elevating effect, were not significantly affected by itraconazole. A counterclockwise hysteresis was evident in the relationship between plasma domperidone and serum prolactin concentrations. Itraconazole shifted the hysteresis to the right. Concentration-effect modeling procedures yielded a significant linear relationship between hypothetical effect site domperidone concentrations and prolactin levels. Itraconazole reduced the slope of the linear relationship. CONCLUSIONS: Itraconazole significantly increased plasma domperidone concentrations. The interaction is probably mainly due to a reduced first pass elimination by inhibition of CYP3A and/or MDR1. The clinical significance of the altered relationship between domperidone concentrations and prolactin levels caused by itraconazole is still to be determined.

Determination of domperidone in human plasma using liquid chromatography coupled to tandem mass spectrometry and its pharmacokinetic study.

A sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of domperidone (CAS number: 57808-66-9) in human plasma using paracetamol (CAS number: 103-90-2) as an internal standard (IS). Domperidone and paracetamol in plasma were extracted with ethyl acetate, separated on a C18 reversed phase column, eluted with mobile phase of acetonitrile-glacial acetic acid (0.3%) (40:60, v/v), ionized by positive ion pneumatically assisted electrospray and detected in the multi-reaction monitoring mode using precursor→product ions of m/z 426.2→175.1 for domperidone and 152→110 for the IS, respectively. The calibration curve was linear (r2≥0.99, n=5) over the concentration range of 0.2-80 ng/mL and with lower limit of detection and quantitation of 0.05 and 0.2 ng/mL. The specificity, matrix effect, recovery, sensitivity, linearity, accuracy, precision, and stabilities were validated for domperidone in human plasma. In conclusion, the validation results showed that this method was sensitive, economical and less toxic and it can successfully fulfill the requirement of clinical pharmacokinetic study of domperidone oral preparation in Chinese healthy volunteers.

Simultaneous determination of omeprazole and domperidone in dog plasma by LC-MS method.

A liquid chromatography coupled with mass spectrometry method was developed and validated to determine omeprazole and domperidone simultaneously in dog plasma. Chromatographic separation was performed on a Narrow Bore C(18) column using methanol-10 mM ammonium acetate (68:32, v/v) as the mobile phase at the flow rate of 0.2 mL/min. The chromatographic separation was achieved in less than 7 min. Diazepam was used as the internal standard. Quantitative analysis was achieved by mass spectrometry detection using a mass spectrometer equipped with an electrospray ionization interface and operated in selected ion monitoring and positive ion mode using target ions at m/z 346 for omeprazole, m/z 426 for domperidone, and m/z 285 for internal standard, respectively. The lower limit of quantification was 1 ng/mL and a linear range of 1-200 ng/mL. The intra- and inter-day relative standard deviation was both less than 10%, and the accuracy values were higher than 90%. The method is sensitive and repeatable enough to be used in pharmacokinetic and bioavailability studies.

Assessing drug distribution in tissues expressing P-glycoprotein using physiologically based pharmacokinetic modeling: identification of important model parameters through global sensitivity analysis.

The structural complexity of a PBPK model is usually accompanied with significant uncertainty in estimating its input parameters. In the last decade, the global sensitivity analysis, which accounts for the variability of all model input parameters simultaneously as well as their correlations, has gained a wide attention as a powerful probing technique to identify and control biological model uncertainties. However, the current sensitivity analysis techniques used in PBPK modeling often neglect the correlation between these input parameters. We introduce a new strategy in the PBPK modeling field to investigate how the uncertainty and variability of correlated input parameters influence the outcomes of the drug distribution process based on a model we recently developed to explain and predict drug distribution in tissues expressing P-glycoprotein (P-gp). As direct results, we will also identify the most important input parameters having the largest contribution to the variability and uncertainty of model outcomes. We combined multivariate random sampling with a ranking procedure. Monte-Carlo simulations were performed on the PBPK model with eighteen model input parameters. Log-normal distributions were assumed for these parameters according to literature and their reported correlations were also included. A multivariate sensitivity analysis was then performed to identify the input parameters with the greatest influence on model predictions. The partial rank correlation coefficients (PRCC) were calculated to establish the input-output relationships. A moderate variability of predicted C(last) and C(max) was observed in liver, heart and brain tissues in the presence or absence of P-gp activity. The major statistical difference in model outcomes of the predicted median values has been obtained in brain tissue. PRCC calculation confirmed the importance for a better quantitative characterisation of input parameters related to the passive diffusion and active transport of the unbound drug through the blood-tissue membrane in heart and brain. This approach has also identified as important input parameters those related to the drug metabolism for the prediction of model outcomes in liver and plasma. The proposed Monte-Carlo/PRCC approach was aimed to address the effect of input parameters correlation in a PBPK model. It allowed the identification of important input parameters that require additional attention in research for strengthening the physiological knowledge of drug distribution in mammalian tissues expressing P-gp, thereby reducing the uncertainty of model predictions.

Population pharmacokinetics of domperidone in preterm neonates.

PURPOSE: A population pharmacokinetic analysis was performed to define domperidone pharmacokinetic parameters in preterm neonates, as no pharmacokinetic data are available in this population. METHODS: An oral domperidone solution was administered (0.75 mg/kg per day) in 32 preterm neonates (64 samples). Domperidone plasma concentration was measured by high-performance liquid chromatography (HPLC) assay, and a one-compartment model with first-order absorption was fitted to the data using NONMEM version V level 1.1. RESULTS: The mean peak and trough plasma concentration values of domperidone were, respectively, 25.3 +/- 20.5 ng/ml and 15.4 +/- 11.4 ng/ml (mean +/- standard deviation). The pharmacokinetic parameters (interindividual variability%) were clearance (Cl/F) = 0.92 L/h (51.6%), volume of distribution (Vd/F) = 0.405 L (68%), and absorption constant rate (Ka) = 0.0843 h(-1) (55.8%). The clearance is not lower than values reported in adults. No influence of covariates (postnatal age, prematurity, weight, gender) on domperidone pharmacokinetic parameters was found. CONCLUSION: This pilot study designed with a limited sampling strategy showed that domperidone plasma concentrations were consistent with those reported in adults, suggesting that domperidone dosage regimen currently used in preterm neonates is suitable.

Quantitative determination of domperidone in human plasma by ultraperformance liquid chromatography with electrospray ionization tandem mass spectrometry.

A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for determining domperidone in human plasma. The analyte and internal standard (IS; mosapride) were isolated from plasma samples by protein precipitation with methanol (containing 0.1% formic acid). The chromatographic separation was performed on an Xterra MS C(18) Column (2.1 x 150 mm, 5.0 microm) with a gradient programme mobile phase consisting of 0.1% formic acid and acetonitrile at a flow rate of 0.30 mL/min. The total run time was 4.0 min. The analyses were carried out by multiple reaction monitoring using the parent-to-daughter combinations m/z 426 --> 175 and m/z 422 --> 198 (IS). The areas of peaks from the analyte and IS were used for quantification of domperidone. The method was validated according to the FDA guidelines on bioanalytical method validation. Validation results indicated that the lower limit of quantification was 0.2 ng/mL, and the assay exhibited a linear range of 0.2-60.0 ng/mL and gave a correlation coefficient (r(2)) of 0.999 or better. Quality control samples (0.4, 0.8, 15 and 50 ng/mL) in six replicates from three different analytical runs demonstrated an intra-assay precision (RSD) 4.43-6.26%, an inter-assay precision 5.25-7.45% and an overall accuracy (relative error) of <6.92%. The method can be applied to pharmacokinetic and bioequivalence studies of domperidone.

Second-derivative synchronous fluorometric method for the simultaneous determination of cinnarizine and domperidone in pharmaceutical preparations. Application to biological fluids.

A rapid, simple and highly sensitive second derivative synchronous fluorometric method has been developed for the simultaneous analysis of binary mixture of cinnarizine (CN) and domperidone (DOM). The method is based upon measurement of the native fluorescence of these drugs at Deltalambda=80 nm in aqueous methanol (50% V/V). The different experimental parameters affecting the native fluorescence of the studied drugs were carefully studied and optimized. The fluorescence-concentration plots were rectilinear over the range of 0.1 to 1.3 microg mL(-1) and 0.1-3.0 microg mL(-1) for CN and DOM, respectively with lower detection limits of 0.017 and 5.77 x 10(-3) microg mL(-1) and quantification limits of 0.058 and 0.02 microg mL(-1) for CN and DOM. The proposed method was successfully applied for the determination of the studied compounds in synthetic mixtures and in commercial tablets. The results obtained were in good agreement with those obtained with reference methods. The high sensitivity attained by the synchronous fluorometric method allowed the determination of CN in real and spiked human plasma. The mean % recoveries in case of spiked human plasma (n=3) were 96.39+/-1.18 while that in real human plasma (n = 3) was 104.67+/-4.16.

Impact of the changes in P-glycoprotein activity on domperidone pharmacokinetics in rat plasma.

The effect of quinidine (QD) and grapefruit juice (GFJ) extract, P-glycoprotein inhibitors, on the domperidone (DOM) concentration in rat plasma was investigated. DOM, a dopamine D(2)-receptor antagonist is a substrate for P-glycoprotein. DOM(10 mg/kg) was administered orally 2 h after GFJ extract (0.2 ml/kg) or QD (25 mg/kg). DOM concentration in plasma samples was determined by HPLC with fluorescence detection. The GFJ extract and QD administration significantly increased c(max) of DOM by 19% and 36%, respectively, and the AUC(0-0.25) (area under the concentration-time curve from time zero to 15 min) by 29% and 44%, respectively. In addition, QD significantly increased the DOM AUC(0-2) (32%), whereas 19% increase was observed after GFJ extract administration. In conclusion, GFJ and QD significantly influenced DOM rat plasma concentration during the first two hours after DOM administration indicating that interaction takes place during absorption phase.

Rapid and sensitive liquid chromatography-tandem mass spectrometry method for the quantitation of domperidone in human plasma.

A rapid and sensitive method for the determination of domperidone in plasma was developed, using high-performance liquid chromatographic separation with tandem mass spectrometry detection. The samples were rendered basic with 1 M Na2CO3 and the domperidone extracted using tert.-butyl methyl ether, followed by back-extraction into formic acid (2% in water). Chromatography was performed on a Phenomenex Luna C8 (2), 5 microm, 150x2 mm column with a mobile phase consisting of acetonitrile-0.02% formic acid (300:700, v/v), delivered at 0.2 ml/min. Detection was performed using an Applied Biosystems Sciex API 2000 mass spectrometer set at unit resolution in the multiple reaction monitoring mode. TurbolonSpray ionisation was used for ion production. The mean recovery of domperidone was +/- 100%, with a lower limit of quantification set at 0.189 ng/ml. This assay method makes use of the increased sensitivity and selectivity of tandem mass spectrometric detection resulting in a rapid (extraction and chromatography) and sensitive method for the determination of domperidone in human plasma, which is more sensitive than previously described methods.