Determination of Domperidone in Human Plasma using Liquid Chromatography Coupled to Tandem Mass Spectrometry and its Pharmacokinetic Study

Abstract

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.

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

“…A liquid chromatography coupled with tandem mass spectrometric (LC‐MS/MS) method providing an LLOQ of 0.189 ng/mL using an 800 μL plasma sample was used for the quantification of domperidone in human plasma (Smit et al ., ). Some other assays based on LC‐MS/MS (Bose et al ., ; Wu et al ., ; Zhang et al ., ) were also described for determining domperidone in human plasma. Xu et al .…”

“…The time for instrumental determination of one sample was only 2.1 min and more than 300 plasma samples could be assayed daily, which makes the method attractive, particularly in high‐throughput bioanalysis of domperidone. The method was proved superior in sensitivity and speed to previously reported methods (Bose et al ., ; Smit et al ., ; Wu et al ., ; Xu et al ., ; Zhang et al ., ) and was fully validated and successfully applied to a pharmacokinetic study in healthy Chinese volunteers after oral administration of a 10 mg domperidone orally disintegrating tablet.…”

Fourth‐derivative synchronous spectrofluorimetry and HPLC with fluorescence detection as two analytical techniques for the simultaneous determination of itopride and domperidone

“…The literature survey revealed that ITP has been determined by spectrophotometry , spectrofluorimetry , high‐performance thin‐layer chromatography (HPTLC) and several HPLC methods using UV , fluorescence , chemiluminescence and MS detection . Several methods have been reported for the determination of DOM including potentiometry , anodic differential pulse voltammetry , HPLC‐MS and HPLC with fluorescence detection . Only one analytical method has been reported for the simultaneous determination of ITP and DOM using HPLC with MS detection .…”

Pharmacokinetics and comparative bioavailability of domperidone suspension and tablet formulations in healthy adult subjects

“…7 The pharmacokinetics (PKs) of domperidone is linear over a dose range of 10-40 mg. 8 It is rapidly absorbed following oral administration with peak plasma concentrations occurring at approximately 30 minutes with drug effect lasts for 4-7 hours. Several analytical methods were developed for the assay of domperidone in human plasma using radioimmunoassay, 8 Clinical Pharmacology in Drug Development 3 (2) HPLC, 10 and LC-MS. [11][12][13][14][15][16] A new and simple validated HPLC assay method for determination of domperidone in human plasma was a prerequisite for the current study. 9 The oral liquid formulations poses an alternative way in providing medications to pediatric patients, geriatric patients, patients with feeding tubes, and patients who cannot swallow solid dosage forms.…”

“…Accordingly, the objective of this research was studying the PK and the comparative bioavailability of domperidone suspension and tablet formulations in fasting, healthy Egyptian male volunteers. Several analytical methods were developed for the assay of domperidone in human plasma using radioimmunoassay, 8 Clinical Pharmacology in Drug Development 3 (2) HPLC, 10 and LC-MS. [11][12][13][14][15][16] A new and simple validated HPLC assay method for determination of domperidone in human plasma was a prerequisite for the current study.…”