Simultaneous Determination Of Metoprolol Research Articles

Extraction and simultaneous determination of metoprolol and α-hydroxy metoprolol in latent fingerprints by liquid chromatography tandem mass spectrometry

A simple extraction and sensitive simultaneous analysis method for metoprolol and its metabolite alpha-hydroxy metoprolol in latent fingerprint using liquid chromatography-mass spectrometry was developed. The extraction procedure was optimized as scrubbing using cotton swabs for 30 times followed by ultrasonic assistance in 30 °C methanol for 5 min with power of 2000 W. Drug analysis was performed using the mixture of methanol and 0.1% formic acid solution (pH 3.5, 30:70, v/v) as the mobile phase under positive electrospray ionization condition. The linear range obtained was 1.0–500.0 ng/mL for MET, and α-MET, and the limit of detection and the limit of quantification were 0.3 ng/cotton swab and 1.0 ng/cotton swab, respectively. The method showed very slight matrix effect and good recovery to the analytes in the fingermarks. Evaluation of extraction substrates and developing methods showed that the method developed is best used for impermeable substrates and that the commercially development powders have very slight influence on the qualitative detection of metoprolol in fingermarks. Finally, the drug users distinguishing test proved that the method developed for pharmaceuticals could be applied in the forensic analysis for circling out the pool of suspects in the criminal investigation based on their drug use history.

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.

Simultaneous Determination of Metoprolol And α-Hydroxymetoprolol in Human Plasma Using Excitation–Emission Matrix Fluorescence Coupled With Second-Order Calibration Methods

Metoprolol (MET) is a β1-adrenoceptor antagonist, which is widely used in the treatment of cardiovascular diseases, and α-hydroxymetoprolol (α-OHM) is its hydroxylated metabolite. Owing to their similar structures, optimization of the condition for the chromatography approach, which is in common use for determination, is both time consuming and laborious. A new and effective strategy that combines the excitation-emission matrix fluorescence with second-order calibration methods was developed for simultaneous determination of MET and α-OHM in human plasma. Although the fluorescence spectra of MET and α-OHM overlapped and a large number of unknown and uncalibrated fluorescent components coexisted, the developed method enables accurate concentrations together with reasonable resolution of excitation and emission profiles for the analytes of interest. An additional advantage of the proposed method is that there is no need for separation and sample pretreatment, in addition to lower cost than traditional methods.

Simultaneous determination of metoprolol and alpha-hydroxymetoprolol in human plasma and urine by liquid chromatography with a preliminary observation on metoprolol oxidation in Japanese subjects.

A simple, sensitive, and highly reliable liquid chromatographic method using fluorescence detection is described for the simultaneous determination of metoprolol and alpha-hydroxymetoprolol in plasma and urine. This method involves a single extraction of the compounds with the internal standard pindolol from alkalinized plasma or urine into dichloromethane. A reconstituted aliquot with a mobile phase is injected onto a reversed-phase, Zorbax ODS column, and the detection is achieved by the excitation and emission wavelengths at 230 and 300 nm, respectively. The assay is reproducible and precise for metoprolol and alpha-hydroxymetoprolol in both plasma and urine samples, as judged by a coefficient of variation of less than 9.2% at all concentrations examined. The standard curves for metoprolol and alpha-hydroxymetoprolol are linear over 10-200 ng/ml in plasma and over 0.5-10 micrograms/ml in urine. The lower detection limit is 2 ng/ml for each of the compounds in plasma using a 0.5-ml sample. Preliminary data on the oxidation polymorphism of metoprolol in Japanese subjects are reported using the current assay method. In 183 Japanese subjects no poor metabolizer of metoprolol has been identified so far.

Simultaneous determination of metoprolol and metabolites in urine by capillary column gas chromatography as oxazolidineone and trimethylsilyl derivatives

A method for the determination of metoprolol and its main metabolises in urine is presented. The method comprises derivatization of the aminopropanol side-chain with phosgene at alkaline pH and isolation in an organic phase at acidic pH. After trimethylsilylation, separation and quantification are performed by capillary column gas chromatography with flame ionization detection. The reaction is performed at pH 12 with 60 μl of 2 M phosgene in toluene added in three portions. Diethyl ether—dichloromethane is used as extraction medium and bis(trimethylsilyl)acetamide as silylating agent. With spiked samples linear standard curves were obtained for metoprolol and three of its main metabolises with a detection limit varying between 4 and 20 μol/l of urine. The method was applied to urine samples from a normal individual who had taken 292 μmol of metoprolol as tartrate.