Development and Validation of Novel UPLC-MS/MS Method for the Analysis of Macitentan in Pharmaceutical Formulations

2019 ◽  
Vol 15 (5) ◽  
pp. 554-559
Author(s):  
Mevlut Albayrak ◽  
Alptug Atila
Keyword(s):  
Atmospheric Pressure Chemical Ionization ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Pharmaceutical Preparations ◽  
Pharmaceutical Formulations ◽  
Ultra Performance Liquid Chromatography ◽  
Pure Form ◽  
Column Temperature ◽  
Limit Of Quantitation

Introduction: Macitentan is an endothelin receptor antagonist drug used in the treatment of pulmonary arterial hypertension. Materials and Methods: A new, sensitive, simple, accurate and rapid ultra-performance liquid chromatography in combination with tandem triple quadruple mass spectrometry (UPLC-MS/MS) method has been developed and validated for the determination of macitentan in pharmaceutical formulations. Macitentan and bosentan which are used as internal standard (IS) were detected using atmospheric pressure chemical ionization (APCI) in positive ion, multiple reaction monitoring (MRM) mode by monitoring mass transitions (precursor to product) m/z 589.1→203.3 and 552.6→311.5, respectively. Chromatographic separation was carried out on reverse phase C18 column (5 µm, 4.6 * 150 mm). Water containing 0.2 % acetic acid in acetonitrile (10:90, v/v) was used as the mobile phase in the isocratic elution. The system was optimized with injection volume of 10 µL, column temperature of 35 °C and flow rate of 1 mL min-1 Retention times were 1.97 min for macitentan and 1.72 min for IS. Results and Discussion: The calibration curve with a high correlation coefficient (0.9997) was linear range 0.5-500 ng mL-1. The lower limit of quantitation (LLOQ) and average recovery values were determined as 0.5 ng mL-1 and 99.7 %, respectively. The developed novel method has been successfully applied for the determination of macitentan in pure form and pharmaceutical formulations. Conclusion: The present method is the first study developed and validated for the determination of macitentan from the pharmaceutical preparations and pure form by UPLC-MS/MS method in the literature.

scholarly journals Development and validation of a gas chromatographic method for the assay of memantine hydrochloride in pure and tablet dosage forms

2011 ◽  
Vol 9 (1) ◽  
pp. 1-8 ◽  
Author(s):  
K. Siddappa ◽  
Metre Mallikarjun ◽  
Tambe Mahesh ◽  
Kote Mallikarjun ◽  
Reddy Chandrakanth
Keyword(s):  
Chromatographic Method ◽  
Internal Standard ◽  
Pharmaceutical Preparations ◽  
Reference Method ◽  
Pharmaceutical Formulations ◽  
Fused Silica ◽  
Column Temperature ◽  
Significant Difference ◽  
Gas Chromatographic Method

A gas chromatographic method has been developed and validated for the determination of memantine hydrochloride (MMT) in pure and pharmaceutical preparations. The detection was carried out using flame ionization detector. Separation was achieved on a DB-624 fused silica packed capillary column (30 m x 0.320 mm x 1.8 ?m). Nitrogen was used as a carrier gas at a flow rate of 40 mL/min. The column temperature was maintained at 300?C while the temperature of injection port and detector were maintained at 270? and 300?C, respectively. Gabapentin (GPN) was used as an internal standard. The procedure gave a linear response over the concentration range of 0.5-3.5 mg/mL with sufficient reproducibility. The method has been applied successfully for the determination of MMT in pure and pharmaceutical formulations. The excipients present in the formulations did not interfere with the assay procedure. The recovery values were found to be in the range of 99.85-100.1% with RSD values less than 1%. The results obtained from this method were compared with the reference method (HPTLC) reported in literature and no significant difference was found statistically.

scholarly journals UPLC–MS/MS simultaneous determination of methamphetamine, amphetamine, morphine, monoacetylmorphine, ketamine, norketamine, MDMA, and MDA in hair

2020 ◽  
Vol 32 (2) ◽  
pp. 145-148 ◽  
Author(s):  
Siyuan Chen ◽  
Jianshe Ma ◽  
Xianqin Wang ◽  
Peiwu Geng
Keyword(s):  
Simultaneous Determination ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Correlation Coefficients ◽  
Ammonium Hydroxide ◽  
Ultra Performance Liquid Chromatography ◽  
Acetate Solution ◽  
Hair Samples ◽  
Relative Standard

Hair is a stable specimen and has a longer detection window (from weeks to months) than blood and urine. Through the analysis of hair, the long-term information of the drug use of the identified person could be explored. Our work is to establish an ultra-performance liquid chromatography–tandem mass spectroscopy (UPLC–MS/MS) method for simultaneous determination of methamphetamine, amphetamine, morphine, monoacetylmorphine, ketamine, norketamine, 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyamphetamine (MDA) in hair. Methoxyphenamine was used as an internal standard. The chromatographic separation was performed on a UPLC ethylene bridged hybrid (BEH) C18 (2.1 mm × 50 mm, 1.7 μm) column using a mobile phase of acetonitrile–water with 10 mmol/L ammonium acetate solution which containing 0.05% ammonium hydroxide. The multiple reaction monitoring in positive electrospray ionization was used for quantitative determination. The intra-day and inter-day precisions (relative standard deviation [RSD]) were below 15%. The accuracy ranged between 85.5% and 110.4%, the average recovery rate was above 72.9%, and the matrix effect ranged between 92.7% and 109.2%. Standard curves were in the range of 0.05–5.0 ng/mg, and the correlation coefficients were greater than 0.995. The established UPLC–MS/MS method was applied to analyze the hair samples successfully.

scholarly journals Pharmacokinetic UPLC–MS/MS studies on byakangelicol after oral and intravenous administration to rats

2020 ◽  
Vol 32 (1) ◽  
pp. 49-52
Author(s):  
Xi Bao ◽  
Bingge Huang ◽  
Yiting Mao ◽  
Zhiguang Zhang ◽  
Yunfang Zhou ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Multiple Reaction Monitoring ◽  
A549 Cells ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Absolute Bioavailability ◽  
Dependent Manner ◽  
Limit Of Quantitation ◽  
Intravenous And Oral Administration

Byakangelicol is one of coumarins from Baizhi and has been shown to inhibit the release of PGE2 from human lung epithelial A549 cells in a dose-dependent manner. A sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed and full validated for the quantification of byakangelicol in rat plasma. The pharmacokinetics of byakangelicol after both intravenous (5 mg/kg) and oral (15 mg/kg) administrations were studied. Chromatographic separation was performed on an ultra-performance liquid chromatography ethylene bridged hybrid (UPLC BEH) C18 column with acetonitrile and 0.1% formic acid as the mobile phase at a flow rate of 0.4 mL/min; fargesin was used as the internal standard (IS). The following quantitative analysis of byakangelicol was utilized in the multiple reaction monitoring mode. The samples were extracted from rat plasma via protein precipitation using acetonitrile. In the concentration range of 1–2000 ng/mL, the method correlated linearity (r > 0.995) with a lower limit of quantitation (LLOQ) of 1 ng/mL. Intra-day precision was less than 11%, and inter-day precision was less than 12%. The accuracy was between 92.0% and 108.7%, the recovery was better than 89.6%, and the matrix effect was between 85.9% and 98.6%. The method was successfully applied to a pharmacokinetic study of byakangelicol after intravenous and oral administration, and the absolute bioavailability was 3.6%.

scholarly journals Development and Validation of New RP-HPLC Method for Simultaneous Determination of Methyl and Propyl Parabens with Levetiracetam in Pure Form and Pharmaceutical Formulation

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Soad S. Abd El-Hay ◽  
Mostafa S. Mohram
Keyword(s):  
High Performance ◽  
Limit Of Detection ◽  
Degradation Products ◽  
Gradient Elution ◽  
Hplc Method ◽  
Pure Form ◽  
Mobile Phase Flow Rate ◽  
Column Temperature ◽  
Limit Of Quantitation

A simple and robust high-performance liquid chromatography (HPLC) method is described for the assay for levetiracetam (LTC), methyl paraben (MHB), and propyl paraben (PHB) either in their pure form or in commercial Levepsy® syrup. The method is selective and stability indicating and all chromatographic conditions were studied to obtain adequate separation of LTC, MHB, and PHB from their degradation products and from excipients. The HPLC separation was carried out on a RP C18 Hypersil BDS analytical column (150 mm × 4.6 mm ID) using gradient elution system. The mobile phase flow rate was 1.5 mLmin−1 and the column temperature was kept at 40°C. Complete separation of the studied components was obtained within a cycle time of 8 min. LTC, MHB, and PHB were eluted at 1.56, 5.86, and 7.85 min, respectively. Detection was carried out at 240 nm using a dual wavelength detector. The method has been validated for linearity, accuracy, precision, specificity, limit of detection, limit of quantitation, robustness, and ruggedness. The proposed method was successfully applied for the determination of LTC in the presence of parabens in Levepsy syrup.

scholarly journals Determination of eugenitin in mouse blood by ultra-performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study

2021 ◽  
Author(s):  
Chongliang Lin ◽  
Dezhen Song ◽  
Haodong Jiang ◽  
Lvqi Luo ◽  
Xi Bao ◽  
...  
Keyword(s):  
Biological Fluids ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Quantitative Detection ◽  
Syzygium Aromaticum ◽  
Mouse Blood ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass

Abstract Eugenitin is a non-volatile chromone derivative which is always found in dried flower buds of Syzygium aromaticum L. (Merr.) & L.M. Perry. Until now, there were no reports about the pharmacokinetics of eugenitin in biological fluids. A UPLC-MS/MS method developed to determine eugenitin in mouse blood. The blood samples were prepared by protein precipitation with acetonitrile. Chrysin (internal standard, IS) and eugenitin were gradient eluted by mobile phase of acetonitrile and water (0.1% formic acid) in a BEH C18 column. The multiple reaction monitoring (MRM) of m/z 221.1→206.0 for eugenitin and m/z 255.1→152.9 for IS with an electrospray ionization (ESI) source was used for quantitative detection. The calibration curve ranged from 0.5 to 500 ng/mL (r > 0.995). The accuracy ranged from 98 to 113%, the precision was less than 12%, and the matrix effect was between 86 and 94%, the recovery was better than 81%. The developed method was successfully used for pharmacokinetics of eugenitin in mice after intravenous (5 mg/kg) and oral (20 mg/kg) administration, and the absolute availability of eugenitin was 12%.

scholarly journals Light scattering detector based on light-emitting diodes-Solar cells for a flow analysis of Warfarin in pure form and pharmaceutical formulations

2021 ◽  
Vol 2063 (1) ◽  
pp. 012006
Author(s):  
Nagham S Turkey ◽  
Jalal N Jeber
Keyword(s):  
Solar Cells ◽  
Light Emitting Diodes ◽  
Control Method ◽  
Potassium Dichromate ◽  
Pharmaceutical Preparations ◽  
Pharmaceutical Formulations ◽  
Pure Form ◽  
Yellow Colour ◽  
Light Emitting

Abstract Continuous turbidimetric analysis (CTA) for a distinctive analytical application by employing a homemade analyser (NAG Dual & Solo 0-180°) which contained two consecutive detection zones (measuring cells 1 & 2) is described. The analyser works based on light-emitting diodes as a light source and a set of solar cells as a light detector for turbidity measurements without needing further fibres or lenses. Formation of a turbid precipitated product with yellow colour due to the reaction between the warfarin and the precipitation reagent (Potassium dichromate) is what the developed method is based on. The CTA method was applied to determine the warfarin in pure form and pharmaceutical formulations in the concentration range from 2.0-16& 0.7-16 mmol/L with 0.58 and 0.55 mmol/L of the limit of detections. The correlation coefficients (r) of the developed method were 0.9977 and 0.9981 for cell 1 and 2 respectively. For validation of proposed method, the ICH guidelines were followed. The developed method was successfully applied for the determination of Warfarin in pure and pharmaceutical preparations. In addition, the method can be considered as a quality control method and conveniently used for routine analysis in laboratories since the method permits quantitatively determination of 60 samples/h.

Rapid determination of patulin in medicinal hawthorn fruits by HPLC-MS/MS

2012 ◽  
Vol 5 (1) ◽  
pp. 31-36 ◽  
Author(s):  
L. Xiang ◽  
Y. Gao ◽  
D. Liu ◽  
M. Yang
Keyword(s):  
Rapid Determination ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Negative Ion ◽  
Liquid Liquid Extraction ◽  
Relative Standard ◽  
Limit Of Quantitation ◽  
Hawthorn Fruit ◽  
Negative Ion Mode

An HPLC-tandem mass spectrometry method was developed for the determination of patulin (PAT) in dried medicinal hawthorn fruit, a well-known traditional medicine in China. Liquid-liquid extraction was applied in the sample preparation. Multiple reaction monitoring was performed at m/z 153/109 for PAT and m/z 317/273 for internal standard zearalenone in the negative ion mode with electrospray ionisation source. Good linearity was achieved when spiked PAT concentrations were in the range of 10-500 μg/kg, with coefficient being 0.9993. The limit of quantitation was 10 μg/kg. The extraction recoveries for the spiked PAT at concentrations of 20, 100 and 400 μg/kg were 64.5%, 64.6% and 63.9%, respectively, with relative standard deviations of 1.25%, 2.82% and 2.61%. The intra-day and inter-day precision were in the range of 2.2-9.6% and 5.9-6.4%. This rapid, sensitive and reliable method was applied in 25 batches of medicinal hawthorn fruit, in which PAT was detected in 8 batches, including those that were baked or charred.

A rapid and selective UPLC-MS/MS assay for accurate analysis of apatinib in rat plasma and its application to a pharmacokinetic study

2020 ◽  
Vol 16 ◽  
Author(s):  
Jinglin Gao ◽  
Zhangying Feng ◽  
Huan Ren ◽  
Mengdi Yu ◽  
Haidong Wang ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Kinase Inhibitor ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Flow ◽  
Treatment Method ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Accurate Analysis ◽  
Limit Of Quantitation

Objective: Apatinib, a novel small-molecule tyrosine kinase inhibitor (TKI), is under development to treat advanced gastric cancer. As to pharmacokinetic evaluation and routine drug monitoring of apatinib, a quantitative ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method in rat plasma was developed with tinidazole used as an internal standard (IS). Method: Protein precipitation (PPT) was selected as a sample pre-treatment method to extract apatinib. Then chromatography was performed on a Kinetex C8 column (2.1×100 mm, 2.6 μm) using a constant mobile phase including 0.2% formic acid and 10 mM ammonium acetate in water and methanol (30:70, v/v) with a gradient flow rate from 0.2 mL/min to 0.4 mL/min. Only 4.5 min was for a total chromatographic analysis. Mass spectrometric detection was carried on positive electrospray ionization (ESI+) mode with multiple-reaction monitoring (MRM). Results: Standard calibration curve showed good linearity in 2-1000 ng/mL with the correlation coefficient (R2) > 0.99. The lower limit of quantitation (LLOQ) was 2 ng/mL. The precision, accuracy, extraction recovery, matrix effect, stability and carryover were all within acceptable range. Conclusion: This method was simple, accurate, selective and successfully used for a pharmacokinetic study following seven rats orally administrated a single of 60 mg/kg apatinib.

scholarly journals Stability Indicating Method for Simultaneous RP HPLC Determination of Camylofin Dihydrochloride and Nimesulide in Pharmaceutical Preparations

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Rajeev Kumar R. Singh ◽  
Manapragada V. Rathnam ◽  
Sangeeta J. Singh ◽  
Raju V. K. Vegesna
Keyword(s):  
Internal Standard ◽  
Pharmaceutical Preparations ◽  
Reversed Phase ◽  
Control Analysis ◽  
Solution Stability ◽  
Buffer Solution ◽  
Solution Ph ◽  
Column Temperature ◽  
Stability Indicating

A simple, fast, and precise reversed phase high-performance liquid chromatographic method has been developed for the simultaneous determination of camylofin dihydrochloride and nimesulide using caffeine as an internal standard. The stability indicating capability of the method was proved by subjecting the drugs to stress conditions as per ICH-recommended test conditions. Separation was achieved using Varian Chromspher 5 C18 column (250 mm × 4.6 mm, 5 μm) as stationary phase with a mobile phase comprising of buffer solution pH 5.0 : methanol (600 : 400, v/v) at a flow rate of 1.0 mL min−1, column temperature of 30∘C and UV detection at 220 nm. The retention time of caffeine, camylofin dihydrochloride, and nimesulide was about 5.0 min, 6.1 min, and 12.7 min, respectively. The proposed method was validated for linearity, accuracy, precision, sensitivity, robustness and solution stability. Linearity, accuracy, and precision were found to be acceptable over the ranges of 250–750 μg mL−1 for Nimesulide and 125–375 μg mL−1 for camylofin dihydrochloride. The test solution was found to be stable for 72 h. It can be conveniently adopted for routine quality control analysis.

scholarly journals Eco-Friendly, Simple, Fast, and Sensitive UPLC-MS/MS Method for Determination of Pexidartinib in Plasma and Its Application to Metabolic Stability

Molecules ◽  
2022 ◽  
Vol 27 (1) ◽  
pp. 297
Author(s):  
Essam Ezzeldin ◽  
Muzaffar Iqbal ◽  
Yousif A. Asiri ◽  
Gamal A. E. Mostafa ◽  
Ahmed Y. A. Sayed
Keyword(s):  
Formic Acid ◽  
Method Validation ◽  
Multiple Reaction Monitoring ◽  
Liver Microsomes ◽  
Internal Standard ◽  
Metabolic Stability ◽  
Methyl Tert Butyl Ether ◽  
Butyl Ether ◽  
Limit Of Quantitation

Pexidartinib is the first drug approved by the U.S. Food and Drug Administration specifically to treat the rare joint tumor tenosynovial giant cell tumor. In the current study, a validated, selective, and sensitive UPLC-MS/MS assay was developed for the quantitative determination of pexidartinib in plasma samples using gifitinib as an internal standard (IS). Pexidartinib and IS were extracted by liquid-liquid extraction using methyl tert-butyl ether and separated on an acquity BEH C18 column kept at 40 °C using a mobile phase of 0.1% formic acid in acetonitrile: 0.1% formic acid in de-ionized water (70:30). The flow rate was 0.25 mL/min. Multiple reaction monitoring (MRM) was operated in electrospray (ESI)-positive mode at the ion transition of 418.06 > 165.0 for the analyte and 447.09 > 128.0 for the IS. FDA guidance for bioanalytical method validation was followed in method validation. The linearity of the established UPLC-MS/MS assay ranged from 0.5 to 1000 ng/mL with r > 0.999 with a limit of quantitation of 0.5 ng/mL. Moreover, the metabolic stability of pexidartinib in liver microsomes was estimated.

Sign in / Sign up

Export Citation Format

Share Document