Method For Determination Of Metoprolol Research Articles

Novel bioanalytical LC-MS/MS method for determination of metoprolol in human plasma

Novel bioanalytical LC-MS/MS method for determination of metoprolol in human plasma

Разработка и валидация методики количественного определения метопролола в плазме крови пациентов методом ВЭЖХ-МС/МС

INTRODUCTION: Metoprolol is a selective β1-adrenoblocker without intrinsic sympathomimetic activity. The effectiveness of metoprolol has been proven in numerous clinical studies in the treatment of arterial hypertension, stable angina, myocardial infarction, chronic heart failure. To improve the efficiency and safety of the therapy, it is advisable to carry out therapeutic drug monitoring of metoprolol, which requires a sensitive method for its quantitative determination. AIM: To develop, validate and test a method for the determination of metoprolol in human plasma using high performance liquid chromatography (HPLC) with tandem mass spectrometric detection (MS/MS). MATERIALS AND METHODS: The work was performed on Ultimate 3000 TSQ Fortis HPLC-MS/MS (Thermo Fisher, USA). For sample preparation, acetonitrile was used with fexofenadine hydrochloride at a concentration of 10 ng/ml as an internal standard, which was added to plasma samples in 3:1 ratio. The volume of the injected sample was 5 μl. Separation was performed on UCT Selectra C18 4.6 mm × 100 mm, 3 um, 100 A column with a similar pre-column at 35°C, in gradient elution mode in proportion of 0.1% formic acid solution/acetonitrile: 0 min — 80%/20%, 0.1 min — 45%/55%, 5 min — 10%/90%, 10 min — 80%/20%, at flow rate of 300 µl/min. Detection was performed in positive electrospray ionization mode, electrospray voltage 4000 V, sheath gas 50 arb, auxiliary gas 10 arb, purge gas 1 arb, evaporator temperature 350°C, ion transport tube temperature 300°C, using the multiple reaction monitoring mode (MRM) at argon flow rate 2 mTorr, 268 m/z → 115.5 m/z, Collision Energy 18 V, Tube lens 95 V, 268 m/z → 191 m/z, Collision Energy 17 V, Tube lens 95 V. The blood plasma of healthy volunteers served as matrix. RESULTS: The analytical range of the technique was 2–1000 ng/ml. The developed technique was tested on a patient with arterial hypertension. During the analysis, an equilibrium concentration of metoprolol of 12.0 ng/ml was detected in the patient's blood plasma (previously, the patient took metoprolol tartrate at a dose of 12.5 mg twice a day for a week), and in 2 hours after taking the drug — 31.0 ng/ml. CONCLUSION: A method for the quantitative determination of metoprolol in human blood plasma using HPLC-MS/MS has been developed, validated and tested.

HPLC method development for determination of metoprolol, telmisartan and cilnidipine simultaneously using response surface design

The development of an HPLC method for determination of Metoprolol, Telmisartan and Cilnidipine simultaneously in additional dosage was not published or reported up till date. The main aim of our study was to design a simultaneous and multiple response optimizations using the Derringer's desirability function in order to estimate Metoprolol, Telmisartan and Cilnidipine in pharmaceutical and bulk drug dosage form by HPLC method with experiment central compositive design (CCD) protocol for the quantitative methods analysis and also for validation of the procedure that is developed as per ICH regulations. An innovative RP-HPLC method had been designed for the estimation of Metoprolol, Telmisartan and Cilnidipine simultaneously in formulation using central composite design. Three factors were investigated and determined as significant when compared to the interaction and quadratic effect of the samples that CCD along with the response of the surface methodology. The developed method produced a good resolution of the drugs with a very short run time of 7.5 min. It was also validated according to ICH guidelines. It was recognized as novel and simple method that is accurate and cost-effective. So the proposed method fits best in the assaying routine of Metoprolol, Telmisartan and Cilnidipine in any formulations produced by quality control laboratories.

Development and validation of a liquid chromatography–mass spectrometry method for simultaneous determination of metoprolol and telmisartan in rat plasma and its application to pharmacokinetic study

A simple, rapid and sensitive high-performance liquid chromatography–tandem mass spectrometry method has been developed and validated according to the Food and Drug Administration (FDA) guidelines for simultaneous determination of metoprolol and telmisartan in rat plasma using atorvastatin as an internal standard. The analytes were separated on a Gemini C18 column (50 mm × 4.6 mm, 5 µm) with an isocratic mobile phase of methanol–water containing 0.5 % formic acid (9:1, v/v) at a flow rate of 0.5 mL/min. The estimation was carried out by triple quadrupole mass spectrometry using electrospray ionization technique, operating in multiple reaction monitoring and positive ion modes. Simple liquid–liquid extraction was used for sample preparation. Linearity was achieved over the concentration range of 1–500 ng/mL for both the analytes in rat plasma. Results of validation parameters of the method were with the acceptance criteria of the FDA guidelines. The method was found suitable to quantitatively assess the pharmacokinetics of metoprolol and telmisartan in rat following administration of a single oral dose 2.5 and 2 mg/kg body weight, respectively in Wistar albino rat.

Pharmacokinetic study of metoprolol in rabbit plasma by capillary electrophoresis with laser-induced Fluorescence detection

This work described a sensitive method for determination of metoprolol in rabbit plasma. The method involved purification by ultrafiltration, derivatization with Fluorescein isothiocyanate, separation by capillary electrophoresis and determination by laser-induced fluorescence detector. Other components in plasma including a variety of amino acids and proteins did not interfere with the determination of metoprolol under experimental conditions. The assay had a wide range (2.0–500 ng/mL) of linearity and a detection limit of 0.8 ng/mL. The intra- and inter-day precisions of the QC samples were satisfactory with RSD less than 10% and accuracy within 10%. This method was successfully applied to pharmacokinetic study of metoprolol in rabbit blood.

Determination of metoprolol in rabbit blood using capillary electrophoresis with laser-induced fluorescence detection

Abstract This work described a sensitive method for determination of metoprolol in rabbit plasma. The method involved purification by ultrafiltration, derivatization with fluorescein isothiocyanate, determination by capillary electrophoresis (CE) coupled with laser-induced fluorescence (LIF) detector. Other components in plasma including a variety of amino acids and proteins did not interfere with the determination of metoprolol in experimental condition. The assay had a wide range (2.0–500 ng/mL) of linearity and a detection limit of 0.8 ng/mL. The intra- and inter-day precisions were satisfactory with relative standard deviation (RSD) less than 10.0% and accuracy within 10.0%. This method was successfully applied to pharmacokinetic study of metoprolol in rabbit blood.

Development and Validation of GC-MS Method for Determination of Metoprolol in Human Urine

This paper describes a specific, sensitive, and accurate gas chromatography-mass spectrometry method for determination of metoprolol in human urine after derivatization with N-Methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA). The method employed a one-step extraction of metoprolol from human urine with a mixture of ethylacetate and diethylether (2:1, v/v) at basic pH using atenolol as internal standard. Calibration curves were linear over the concentration range 50–3000 ng/mL. Intra- and inter-day precision values for metoprolol in human urine were less than 6.0%. The analytical recovery of metoprolol from human urine averaged 90.88%. The limits of detection and quantification of metoprolol were 5.0 and 15 ng/mL, respectively. Also, the developed and validated method was successfully applied to a patient with hypertension who had been given an oral tablet of 100 mg metoprolol.

Gas chromatography–mass spectrometry method for determination of metoprolol in the patients with hypertension

A sensitive and efficient method was developed for determination of metoprolol in human plasma by gas chromatography–mass spectrometry (GC–MS). Metoprolol and atenolol (internal standard, IS) were extracted from human plasma with a mixture of ethylacetate and diethylether at basic pH with liquid–liquid extraction. Calibration curves were linear over the concentration range 15–500 ng/ml. Intra- and inter-day precision values for metoprolol in human plasma were less than 6.4, and accuracy (relative error) was better than 8.8%. The analytical recovery of metoprolol from human plasma averaged 91.20%. The limits of detection (LOD) and quantification (LOQ) of metoprolol were 5.0 and 15 ng/ml, respectively. Also the developed and validated GC–MS method was successfully applied to three patients with hypertension who had been given an oral tablet of 100 mg metoprolol.