Quantitative analysis of Loperamide hydrochloride in the presence its acid degradation products

Hemijska industrija (Impact Factor: 0.36). 01/2009; 63(1). DOI: 10.2298/HEMIND0901039S
Source: DOAJ


The aim of this work was to develop a new RP-HPLC method for the determination of loperamide hydrochloride in the presence of its acid degradation products. Separation of loperamide from degradation products was performed using ZORBAX Eclipse XDB C-18, column with a mobile phase consisting of 0.1% sodium-octansulphonate, 0.05% triethylamine, 0.1% ammonium hydroxide in water:acetonitrile (45:55 v/v). The mobile phase was adjusted to pH 3.2 with phosphoric acid. The method showed high sensitivity with good linearity over the concentration range of 10 to 100 μg cm-3. The method was successfully applied to the analysis of a pharmaceutical formulation (Loperamide, Zdravlje-Actavis, Serbia) containing loperamide hydrochloride with excellent recovery. The loperamide hydrochloride degradation during acid hydrolysis and kinetics investigation was carried out in hydrochloric acid solutions of 0.1, 1.0 and 1.5 mol dm-3, at different temperatures (25 and 40°C), by monitoring the parent compound itself. The first order reaction of loperamide degradation in acid solution was determined. The activation energy was estimated from the Arrhenius plot and it was found to be 38.81 kJ mol-1 at 40°C. The developed procedure was successfully applied for the rapid determination of loperamide hydrochloride in pharmaceutical formulation (Loperamide, Zdravlje-Actavis, Serbia) and in the presence of its acid degradation products.

Download full-text


Available from: Ivan M. Savic, Apr 09, 2015
  • Source
    • "In humans, following oral administration of loperamide solid formulations, about 50% of the administered loperamide is absorbed in the gastrointestinal tract, absorbance occurring within 1 h in high bounding percent to plasma proteins (95%) [8], at maximum concentration time of 6 h and half-life around 11 h [9], but only a little intact drug (1%) reaches systemic circulation, due to its extensive first pass metabolism [6] [7]. Loperamide determination in human body makes challenging work in bioavailability and bioequivalence research field, due to its low availability in plasma and low doses [6] [7], in pharmaceutical industries and in vitro studies, loperamide has been determined by HPLC easily [10] [11] [12] [13] [14], and more sensitive methods were required for in vivo determinations, as in rats by HPLC–UV [15] and HPLC–ECD [16]. In human body there were many determinant studies of loperamide by using LC-tandem MS [17] [18] [19] [20], but more sensitive bioanalytical methods with easier http://dx.doi.org/10.1016/j.jchromb.2014.09.037 1570-0232/© 2014 Elsevier B.V. All rights reserved. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A simple and sensitive liquid chromatography-tandem mass spectrometric method for quantification of loperamide in human plasma and saliva was developed and validated, and then successfully applied in pharmacokinetic clinical study to investigate and correlate bioavailability of Imodium (R) 2 mg quartet tablet dose in both human plasma and saliva. Loperamide with labeled internal standard was extracted from its biological matrix by methanol as protein direct precipitant in single extraction step. Adequate chromatographic separation for analytes from plasma and saliva matrices was achieved using ACE C18 (50mm x 2.1 mm, 5 mu m) column, eluted by water/methanol/formic acid (30:70:0.1%, v/v), delivered isocratically at constant flow rate of 0.75 ml/min. The method validation intends to investigate specificity, sensitivity, linearity, precision, accuracy, recovery, matrix effect and stability according to European guideline, and partial validation was applied on saliva, specificity, matrix effect, recovery, sensitivity, within and between day precision and accuracy. The calibration curve was linear through the range of 20-3000 pg/ml in both plasma and saliva using a 50 mu l sample volume. The partial validation sections outcome in saliva was so close to those in plasma. The within- and between-day precisions were all below 8.7% for plasma and below 11.4% for saliva. Accuracies ranged from 94 to 105% for both matrices. In this study, 26 healthy volunteers participated in the clinical study, and 6 of gave their saliva samples in addition to plasma at the same time schedule. The pharmacokinetic parameters of C-max, AUC(0-t) and AUC(0-infinity), T-max and T-1/2 in both plasma and saliva were calculated and correlated.
    Journal of Chromatography B 12/2014; 972. DOI:10.1016/j.jchromb.2014.09.037 · 2.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Two simple, economical, precise and reproducible visible spectrophotmetric methods have been developed for the estimation of loperamide hydrochloride in tablet formulation. The developed methods are based on the formation of chloroform extractable complex of loperamide hydrochloride with bromo phenol blue and thymol blue in double distilled water. The complex with bromo phenol blue (method I) shows absorbance maxima at 421.8 nm and linearity in the concentration range of 5-40 μg/ml. The extracted complex with thymol blue (Method II) shows absorbance maxima at 437.8 nm and the linearity in the concentration range of 10-100 μg/ml. Results of analysis for both the methods were validated statistically and by recovery studies.
    Asian Journal of Pharmaceutical and Clinical Research 04/2010; 3(2):121-122.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent years have seen an ever increasing interest in application of novel materials in solid dosage form. Loperamide hydrochloride [4-(pchlorophenyl)- 4-hydroxy-N, N-dimethyl-diphenyl-1-piperidine butyramide hydrochloride], is an opiate agonist widely used as an effective drug for the control and symptomatic relief of acute non-specific diarrhea. The present work aimed to prepare Loperamide hydrochloride chewable tablet in combined with simethicone and develop a new sensitive and specific analytical procedure by HPLC suitable for application in a drug quality control. Loperamide chewable tablets were prepared by wet granulation technique and it has been found that the prepared tablets showed good physical characteristics, drug content and percentage of drug release. Among the 6 formulations F 1 showed better drug release (96%) and drug content (98.38%) than other formulations. Method of non-aqueous granulation and adsorption of simethicone to dry powder blend improved hardness and provides good physical appearance to the tablets. Addition of Loperamide hydrochloride to binder solution and using proper amount of surfactant (SLS) increased content uniformity and better dissolution of Loperamide hydrochloride. Further, F 1 was selected for the method development and validation purpose. The validation data indicates the suitability of the developed chromatographic method which is easier and cost effective than the other reported and official methods.
    International Journal of Pharmacy and Pharmaceutical Sciences 01/2012; 4(2):372-376. · 1.59 Impact Factor