Development and validation of an HPLC-UV method for accelerated stability study and pharmacokinetic analysis of venlafaxine

Abstract

A reverse phase high performance liquid chromatography method has been developed and validated for accelerated stability study and determination of pharmacokinetic parameters of venlafaxine HCl. The chromatographic separation was carried out using ODS analytical column (250 × 4.6 mm i.d., 5 μm particle size). The mobile phase included acetonitrile, methanol and potassium dihydrogen phosphate buffer (30:30:40; pH 6.1) at a flow rate 1.5 mL min −1 . UV-Visible detector was used at wavelength of 227 nm to monitor elutions. Retention time observed was 2.745 min. The method was validated for linearity, accuracy, precision, sensitivity and robustness. Accelerated stability study of venlafaxine HCl capsules was carried out at 40 and 50 °C under 75% RH level. Suggested method was successfully applied for the pharmacokinetic analysis of venlafaxine hydrochloride tablets. Each of ten albino rabbits (≈ 1.2 kg each) was orally administered with 5 mg dose of venlafaxine HCl. The method was proved to be linear (R 2 >0.998), accurate (98.25-99.27%), sensitive (LOD: 35ngmL −1 ; LOQ: 105 ng mL −1 ) and robust (RSD<1%). The drug showed stability at accelerated conditions of temperature and humidity. The main pharmacokinetic parameters of tested products were as follows: t max was 2.5h, C max was 56.5 μg mL −1 , t 1/2 was 8.2 h, AUC 0-36 was 845.9 μg h mL −1 . The developed method is suitable to apply for quality control analysis and pharmacokinetic studies.

Tandem Mass Spectrometry (MS/MS) in the Preclinical Pharmacokinetic Study of a Highly Prescribed SNRI Drug for Depression and Its Application to Oral Extended Release Solid Dosage Formulations in Rabbits

“…Ali et al (2019) has also employed an HPLC-UV method for pK studies of VEN containing oral solution and sustained release hydrogel composites in rabbits 43 . An HPLC-UV method developed and validated in rabbit plasma by Sher et al (2020) has been applied to pK analysis of VEN in albino rabbits after its oral administration 44 .…”

Quantitative determination of the content of venlafaxine and its active metabolite in human plasma using liquid chromatography-mass spectrometry

“…Для анализа венлафаксина и его активного метаболита доступно множество методов: газовая хроматография c масс-спектрометрией (ГХ-МС) [12], высокоэффективная жидкостная хроматография (ВЭЖХ) с УФ-детекцией [13], ВЭЖХ с флуоресцентной детекцией [14], а также применяется ВЭЖХ с тандемной массспектрометрией (ВЭЖХ-МС/МС) [15]. При этом некоторые методики не подходят для ТЛМ из-за недостаточной чувствительности, другие требуют сложную многоступенчатую очистку и дериватизациюдорогостоящие и отнимающие много времени подходы.…”

Multiple-reaction monitoring (MRM) LC–MS/MS quantitation of venlafaxine and its O-desmethyl metabolite for a preclinical pharmacokinetic study in rabbits

“…Ali et al has also employed an HPLC–UV method for PK studies of VEN containing oral solution and sustained release hydrogel composites in rabbits 42 . An HPLC–UV method developed and validated in rabbit plasma by Sher et al has been applied to PK analysis of VEN in albino rabbits after its oral administration 43 .…”