Liquid Chromatography-Electrospray Quadrupole Linear Ion Trap Mass Spectrometric Method for Quantitation of Domperidone in Chinese Healthy Volunteers

A rapid,sensitive,and accurate method based on LC/MS/MS was developed and validated for the determination of domperidone in human plasma.Domperidone and internal standard,tramadol,were extracted from plasma with diethyl ether-dichloromethane(60∶40,volume ratio)and separated by reversed-phase HPLC with methanol-water-ammonia solution(80∶20∶0.2,volume ratio)as the mobile phase.Detection was carried out via multiple-reaction monitoring(MRM)on a Q-trapTM LC/MS/MS system(Q-trapTM).The assay result was linear over a concentration range of 0.1-30 ng/mL with a limit of quantitation(LOQ)of 0.1 ng/mL.The inter-and intra-day precision levels were within 7.52% and 12.9%,respectively,whereas the accuracy was within a range of 87.3%-114%.This method has been successfully applied to evaluate the pharmacokinetics of domperidone in Chinese healthy volunteers given an oral dose of 10 mg.     

纳米银参与的多潘立酮化学发光分析法研究

在碱性介质中,基于多潘立酮对纳米银(AgNPs)增敏Luminol-KMnO4化学发光体系发光信号的抑制作用,结合流动注射技术,提出了测定多潘立酮的化学发光分析新方法。在选定的流路和实验条件下,该方法测定多潘立酮的线性范围为1.0×10-8~5.0×10-6 g/mL,检出限为1.05×10-9 g/mL。对1.0×10-6 g/mL的多潘立酮溶液平行测定11次,其相对标准偏差(RSD)为1.7%。该法灵敏、准确、快速,用于样品中多潘立酮的测定,结果满意。     

Analysis of domperidone in pharmaceutical formulations and wastewater by differential pulse voltammetry at a glassy-carbon electrode

The redox characteristics of the drug domperidone at a glassy-carbon electrode (GCE) in aqueous media were critically investigated by differential-pulse voltammetry (DPV) and cyclic voltammetry (CV). In Britton–Robinson (BR) buffer of pH 2.6–10.3, an irreversible and diffusion-controlled oxidation wave was developed. The dependence of the CV response of the developed anodic peak on the sweep rate (ν) and on depolizer concentration was typical of an electrode-coupled chemical reaction mechanism (EC) in which an irreversible first-order reaction is interposed between the charges. The values of the electron-transfer coefficient (α) involved in the rate-determining step calculated from the linear plots of E _p,a against ln (ν) in the pH range investigated were in the range 0.64 ± 0.05 confirming the irreversible nature of the oxidation peak. In BR buffer of pH 7.6–8.4, a well defined oxidation wave was developed and the plot of peak current height of the DPV against domperidone concentration at this peak potential was linear in the range 5.20 × 10⁻⁶ to 2.40 × 10⁻⁵ mol L⁻¹ with lower limits of detection (LOD) and quantitation (LOQ) of 6.1 × 10⁻⁷ and 9.1 × 10⁻⁷ mol L⁻¹, respectively. A relative standard deviation of 2.39% (n = 5) was obtained for 8.5 × 10⁻⁶ mol L⁻¹ of the drug. These DPV procedures were successfully used for analysis of domperidone in the pure form (98.2 ± 3.1%), dosage form (98.35 ± 2.9%), and in tap (97.0 ± 3.6%) and wastewater (95.0 ± 2.9%) samples. The method was validated by comparison with standard titrimetric and HPLC methods. Acceptable error of less than 3.3 % was also achieved. Figure In aqueous media at pH 7.6- 8.4, the DPV and cyclic voltammetry of the drug domperidone (I) at GCE showed an irreversible and diffusion controlled oxidation wave. The values of the electron transfer coefficient (α) involved in the rate determining step were found in the range 0.64± 0.05 confirming the irreversible nature of the peak. The analysis of the drug in pure form and in wastewater samples was successfully achieved     

Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods

Domperidone is a dopamine D₂ receptor antogonist, which has been used as antiemetic agent in human beings. It has been found in wastewater released by some pharmaceutical industries leading to the contamination of surface and ground water. Therefore, a sensitive, inexpensive and reproducible HPLC-SPE method was developed for the analysis of domperidone in the wastewater. The column used was Waters symmetry C₁₈ (15 cm × 0.46 mm, 5 μm). The mobile phase used was phosphate buffer (50 mM, pH 3.5) acetonitrile (80:20, v/v) at the flow rate 2.0 mL/min. The detection was achieved by using UV mode at 230 nm. The retention, separation and resolution factors were 2.63, 3.00 and 3.20, respectively. The percentage recovery of domperidone from wastewater was 95.0%. Celiprolol was used as the internal standard to access the percentage extraction of domperidone from wastewater.     

流动注射化学发光法测定吗丁啉

在碱性条件下 ,H2 O2 氧化鲁米诺产生化学发光 ,吗丁啉对该体系的化学发光具有显著的增敏作用。基于此 ,建立了一种直接测定吗丁啉的流动注射化学发光分析法。该方法的线性范围在 1 .0× 1 0 -6～ 3.0× 1 0 -8g mL ,检出限 ( 3σ)为 5 .0× 1 0 -9g mL ,相对标准偏差为 2 .9% (n =1 1 ) ,已用于吗丁啉片剂及血清中吗丁啉的分析。     

HPLC-MS/MS检测人血浆中多潘立酮

用HPLC-MS/MS测定人血浆中多潘立酮的浓度。采用Luna C18色谱柱（150mm×2mm,5μm）,流动相为甲醇∶水（0.04%醋酸铵）=85∶15（V∶V）,采用选择反应监测（SRM）模式。多潘立酮在0.5—100ng/mL浓度范围内有良好的线性关系,日内、日间相对标准偏差（RSD）和准确度误差（RE）均小于10%。该方法灵敏、准确、快速,已用于人血浆中多潘立酮浓度的检测。     

Boronate-Containing Copolymer Grafted on Eupergit C as Matrix for Affinity Chromatography: Isotherms and Kinetics Study

A stability-indicating HPLC method has been developed and subsequently validated for the simultaneous determination of domperidone and pantoprazole in commercial tablets. The proposed HPLC method utilizes Phenomenex^® Gemini C₁₈ column (150 mm × 4.6 mm i.d., 5 μm) and mobile phase consisting of methanol-acetonitrile-20 mM dipotassium hydrogen phosphate and phosphoric acid buffer pH 7.0 (20:33:47, v/v/v) at a flow rate of 1.19 mL min^?1. Quantitation was achieved with UV detection at 285 nm based on peak area with linear calibration curves at concentration ranges 0.5–5.0 μg mL^?1 for domperidone and 1.0–10 μg mL^?1 for pantoprazole (R ² > 0.999 for both drugs). The method was validated in terms of accuracy, precision, linearity, limits of detection, limits of quantitation and robustness. This method has been successively applied to pharmaceutical formulation and no interference from the tablet excipients was found. Domperidone, pantoprazole and their combination drug product were exposed to acid, base and neutral hydrolysis, oxidation, dry heat and photolytic stress conditions and the stressed samples were analyzed by the proposed method. As the proposed method could effectively separate the drug from its degradation products, it can be employed as stability-indicating method for the determination of instability of these drugs in bulk and commercial products.     

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 Δλ = 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 μg mL⁻¹ and 0.1–3.0 μg mL⁻¹ for CN and DOM, respectively with lower detection limits of 0.017 and 5.77 × 10⁻³ μg mL⁻¹ and quantification limits of 0.058 and 0.02 μg 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.     

LC–ESI/MS Analysis of Levodopa and Methyldopa (IS) in Beagle Dog Pharmacokinetic Study after Oral Administration and Domperidone Given in Advance

A simple, sensitive and accurate method was developed for the quantification of levodopa and methyldopa (IS) in beagle dog plasma by LC–ESI/MS, chromatographic separation was carried out by a Diamonsil C18 column (150 mm × 4.6 mm i.d., 5 mm) with an ODS guard column maintained at 30 °C. The mobile phase was methanol (A) and 0.5% formic acid aqueous solution (B) system in the gradient elution profile, the retention time of levodopa and IS were 4.8 and 6.1 min, respectively, linear range for levodopa concentration was 0.08‐20.0 μg/mL in plasma samples with a correlation coefficient(r) of 0.9978, the limit of detection was 32 ng/mL. CV of intra‐day and inter‐day assays were all less than 15%, mean recoveries of levodopa were all more than 90% in 0.32, 1.6 and 16.0 μg/mL concentrations of levodopa (n = 3). The validated method was successfully applied to the determination of levodopa in plasma samples, pharmacokinetic of levodopa following a single oral dose of compound levodopa tablets and antiemetic drug – domperidone administrated to beagle dogs has been carried out, the main pharmacokinetic parameters of levodopa with domperidone were as follows: T_max (0.50 ± 0.18) h, C_max (39.72 ± 7.91) μg/mL, t_l/2 (0.65 ± 0.07) h, AUC_o‐t (49.01 ± 12.13) μg·h/mL , AUC_o‐∞ (49.10 ± 12.16) μg·h/mL, we also evaluated the effect of domperidone on pharmacokinetics of levodopa in beagle dog. We thought non‐oral sustained‐release formulations should be a very good choice instead of this common oral dosage forms on the market, the test results can provide a reference for clinical trials on drug therapy of Parkinson‘s disease.