scholarly journals Application of 19F NMR Spectroscopy for Content Determination of Fluorinated Pharmaceuticals

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Alex O. Okaru ◽  
Tobias S. Brunner ◽  
Svenja M. Ackermann ◽  
Thomas Kuballa ◽  
Stephan G. Walch ◽  
...  
Keyword(s):  
Spectroscopic Method ◽  
Internal Standard ◽  
High Specificity ◽  
Selective Determination ◽  
Relative Standard ◽  
Fit For Purpose ◽  
Quantitative Nuclear Magnetic Resonance ◽  
Sample Measurement ◽  
Interday Precision

A simple, rapid, and selective quantitative nuclear magnetic resonance spectroscopic method was evaluated for the determination of the content of fluorinated pharmaceuticals. 19F NMR spectra were either obtained in dimethylsulfoxide-d6 or aqueous buffer, using trifluoroacetic acid as internal standard. Quantification of 13 fluorine-containing pharmaceuticals spanning various pharmacological classes was accomplished using the proposed method. The method was found to be fit for purpose (interday precision 1.2% relative standard deviation) and may thus be applied for routine analysis and quality control of fluorine-containing pharmaceuticals due to its simplicity, nondestructive sample measurement, reliability, and high specificity. Therefore, 19F NMR may serve as a suitable analytical tool for the identification and selective determination of fluorinated pharmaceuticals used as reference materials and bulk samples.

Development of a quantitative NMR spectroscopic method for direct and simultaneous determination of four flavonoids in Scutellaria baicalensis Georgi extracts

2019 ◽  
Vol 16 ◽  
Author(s):  
Feng Su ◽  
Ji-Peng Chen ◽  
Pei-Xi Zhu ◽  
Yi-Fan Wang ◽  
Xian-Rui Liang ◽  
...  
Keyword(s):  
Spectroscopic Method ◽  
Internal Standard ◽  
Scutellaria Baicalensis ◽  
Sample Tube ◽  
Relative Peak Area ◽  
Scutellaria Baicalensis Georgi ◽  
Quantitative Nuclear Magnetic Resonance ◽  
Main Components ◽  
Different Origins

: Scutellaria Baicalensis Georgi (SBG), a traditional Chinese medicine (TCM) used for the treatment of antiviral therapy, contains many flavonoids. A simple, fast and accurate 1H quantitative nuclear magnetic resonance (1H-qNMR) method was established for simultaneously determination of four flavonoids (Baicalin, Baicalein, Wogonin and Wogonoside) in SBG extract by using 3,4,5-trichloropyridine as an internal standard (IS). All the NMR determination work was performed at 308 K on an NMR sample tube inserted with a co-axial tube. The NMR sample tube was added with the sample (SBG extract and IS), the co-axial insert tube was added with D2O. Quantification of four flavonoids was carried out by calculating the relative peak area ratio of the selected proton signals from the target compounds and the IS. The validated 1H-qNMR method was successfully used to determine the four flavonoids in 9 batches of SBG from different origins and the results were in good accordance with those obtained from HPLC. The established 1H-qNMR method could be used as a powerful tool for the quality control of SBG from different sources and had potential in the quantification of main components from other TCMs.

Toward absolute methods in clinical chemistry: application of mass fragmentography to high-accuracy analyses.

1976 ◽  
Vol 22 (11) ◽  
pp. 1789-1801 ◽  
Author(s):  
I Björkhem ◽  
R Blomstrand ◽  
O Lantto ◽  
L Svensson ◽  
G Ohman
Keyword(s):  
Clinical Chemistry ◽  
Internal Standard ◽  
High Specificity ◽  
Mass Fragmentography ◽  
Reference Methods ◽  
Relative Standard ◽  
High Degree ◽  
Definitive Methods ◽  
Very High

Abstract We review recently developed reference methods based on mass fragmentography (specific ion monitoring) with use of isotope-labeled internal standard, for determination of cholesterol, triglycerides, urea, glucose, cortisol, progesterone, and testosterone. With an optimal ratio between standard and material to be determined, the relative standard deviation of these methods, based on duplicate determinations, is between 1.3 and 2.7%. The very high specificity of the methods, in combination with the fact that the ratio between labeled and unlabeled molecules is determined with a high degree of accuracy, makes it likely that the most significant errors in the methods are related to errors in pipetting. The possibility is discussed that these methods might be developed into "absolute" or "definitive" methods by subjecting each individual step in the determination to a detailed analysis with respect to possible error. We also discuss some of the consequences of the different reference methods on the choice of routine methods.

ICH/FDA Guidelines-Compliant Validated Stability-Indicating HPLC-UV Method for the Determination of Axitinib in Bulk and Dosage Forms

2020 ◽  
Vol 16 (8) ◽  
pp. 1106-1112
Author(s):  
Ibrahim A. Darwish ◽  
Nasr Y. Khalil ◽  
Mohammad AlZeer
Keyword(s):  
High Performance ◽  
Kinase Inhibitor ◽  
Degradation Products ◽  
Internal Standard ◽  
Dosage Forms ◽  
Uv Detector ◽  
Stability Indicating ◽  
Therapeutic Benefits ◽  
Relative Standard

Background: Axitinib (AXT) is a member of the new generation of the kinase inhibitor indicated for the treatment of advanced renal cell carcinoma. Its therapeutic benefits depend on assuring the good-quality of its dosage forms in terms of content and stability of the pharmaceutically active ingredient. Objective: This study was devoted to the development of a simple, sensitive and accurate stabilityindicating high-performance liquid chromatographic method with ultraviolet detection (HPLC-UV) for the determination of AXT in its bulk and dosage forms. Methods: Waters HPLC system was used. The chromatographic separation of AXT, internal standard (olaparib), and degradation products were performed on the Nucleosil CN column (250 × 4.6 mm, 5 μm). The mobile phase consisted of water:acetonitrile:methanol (40:40:20, v/v/v) with a flow rate of 1 ml/min, and the UV detector was set at 225 nm. AXT was subjected to different accelerated stress conditions and the degradation products, when any, were completely resolved from the intact AXT. Results: The method was linear (r = 0.9998) in the concentration range of 5-50 μg/ml. The limits of detection and quantitation were 0.85 and 2.57 μg/ml, respectively. The accuracy of the method, measured as recovery, was in the range of 98.0-103.6% with relative standard deviations in the range of 0.06-3.43%. The results of stability testing revealed that AXT was mostly stable in neutral and oxidative conditions; however, it was unstable in alkaline and acidic conditions. The kinetics of degradation were studied, and the kinetic rate constants were determined. The proposed method was successfully applied for the determination of AXT in bulk drug and dosage forms. Conclusions: A stability-indicating HPLC-UV method was developed and validated for assessing AXT stability in its bulk and dosage forms. The method met the regulatory requirements of the International Conference on Harmonization (ICH) and the Food and Drug Administration (FDA). The results demonstrated that the method would have great value when applied in quality control and stability studies for AXT.

Development and Validation of a New Method for the Determination of Anti-hepatitis C Agent Simeprevir in Human Plasma using HPLC with Fluorescence Detection

2020 ◽  
Vol 16 (4) ◽  
pp. 428-435
Author(s):  
Ahmed F.A. Youssef ◽  
Yousry M. Issa ◽  
Kareem M. Nabil
Keyword(s):  
Hepatitis C ◽  
Human Plasma ◽  
Fluorescence Detection ◽  
Internal Standard ◽  
Protein Precipitation ◽  
Assay Method ◽  
Fluorescence Detector ◽  
Limit Of Quantification ◽  
Relative Standard

Background: Simeprevir is one of the recently discovered drugs for treating hepatitis C which is one of the major diseases across the globe. Objective: The present study involves the development of a new and unique High-Performance Liquid Chromatography (HPLC) method using fluorescence detection for the determination of simeprevir (SIM) in human plasma. Methods: Two methods of extractions were tested, protein precipitation using acetonitrile and liquidliquid extraction. A 25 mM dipotassium hydrogen orthophosphate (pH 7.0)/ACN (50/50; v/v), was used as mobile phase and C18 reversed phase column as the stationary phase. The chromatographic conditions were optimized and the concentration of simeprevir was determined by using the fluorescence detector. Cyclobenzaprine was used as an internal standard. Results: Recovery of the assay method based on protein precipitation was up to 100%. Intra-day and inter-day accuracies range from 92.30 to 107.80%, with Relative Standard Deviation (RSD) range 1.65-8.02%. The present method was successfully applied to a pharmacokinetic study where SIM was administered as a single dose of 150 mg SIM/capsule (Olysio®) to healthy individuals. Conclusion: This method exhibits high sensitivity with a low limit of quantification 10 ng mL-1, good selectivity using fluorescence detection, wide linear application range 10-3000 ng mL-1, good recovery and highly precise and validation results. The developed method can be applied in routine analysis for real samples.

scholarly journals Quantitative Determination of Azithromycin in Human Plasma by Liquid Chromatography–Mass Spectrometry and its Application in Pharmackokinetic Study

2012 ◽  
Vol 11 (1) ◽  
pp. 55-63 ◽  
Author(s):  
Maizbha Uddin Ahmed ◽  
Mohammad Safiqul Islam ◽  
Tasmin Ara Sultana ◽  
AGM Mostofa ◽  
Muhammad Shahdaat Bin Sayeed ◽  
...  
Keyword(s):  
Mobile Phase ◽  
Solid Phase ◽  
Internal Standard ◽  
Extraction Process ◽  
Serum Samples ◽  
Limit Of Quantification ◽  
Relative Standard ◽  
Linear Concentration Range ◽  
Linear Concentration

Azithromycin is an effective and well-known antimicrobial agent. In the present study, a simple, sensitive and specific LC/MS/MS method has been developed and validated for the quantification of Azithromycin in  human serum samples using Clarithromycin as internal standard. Azithromycin was extracted from biological matrix  by using solid phase extraction process. The chromatographic separation was performed on Luna C18 (3 ?, 2x150   mm) column with a mobile phase consisting of 35 mM ammonium acetate buffer (mobile phase-A) and acetonitrile  and methanol in ratio of 90:10 ( as mobile phase-B) at a flow rate of 0.25 mL/min. The method was validated over a  linear concentration range of 0.5?50.0 ng/mL and limit of quantification (LOQ) was 0.5 ng/mL with a coefficient of  correlation (r2) = 0.9998. The intra-day and inter-day precision expressed as relative standard deviation were 1.64% – 8.43% and 2.32% – 9.92%, respectively. The average recovery of azithromycin from serum was 98.11%. The method  was successfully applied to a pharmacokinetic study after oral administration of Azithromycin 200 mg/5 ml suspension in healthy Bangladeshi volunteers. DOI: http://dx.doi.org/10.3329/dujps.v11i1.12488 Dhaka Univ. J. Pharm. Sci. 11(1): 55-63, 2012 (June)

scholarly journals Determination of 1,3-Dichloropropanol in Soy Sauce and Related Products by Headspace Gas Chromatography with Mass Spectrometric Detection: Interlaboratory Study

2005 ◽  
Vol 88 (5) ◽  
pp. 1404-1412 ◽  
Author(s):  
Sarah Hasnip ◽  
Colin Crews ◽  
Nicholas Potter ◽  
Paul Brereton ◽  
Henri Diserens ◽  
...  
Keyword(s):  
Gas Chromatography ◽  
Standard Deviation ◽  
Relative Standard Deviation ◽  
Internal Standard ◽  
Mass Spectrometric ◽  
Soy Sauce ◽  
Headspace Gas Chromatography ◽  
Relative Standard ◽  
Headspace Gas

Abstract An interlaboratory study was performed to evaluate the effectiveness of a headspace gas chromatography (GC) method for the determination of 1,3-dichloro-propan-2-ol (1,3-DCP) in soy sauce and related products at levels above 5 ng/g. The test portion is mixed with an internal standard (d5-1,3-DCP) and ammonium sulfate in a sealed headspace vial. After achieving equilibrium, the headspace is sampled either by gas-tight syringe or solid-phase microextraction (SPME) and analyzed by GC with mass spectrometric detection. 1,3-DCP is detected in the selected-ion mode (monitoring m/z 79 and 81 for 1,3-DCP and m/z 82 for the deuterated internal standard) and quantified by measurement against standards. Test materials comprising soy, dark soy, mushroom soy, and teriyaki sauces, both spiked and naturally contaminated, were sent to 9 laboratories in Europe, Japan, and the United States; of these, 5 used SPME and 4 used syringe headspace analysis. Test portions were spiked at 5.0, 10.0, 20.0, 100.0, and 500.0 ng/g. The average recovery for spiked blank samples was 108% (ranging from 96–130%). Based on results for spiked samples (blind pairs at 5, 10, 20, 100, and 500 ng/g) as well as a naturally contaminated sample (split-level pair at 27 and 29 ng/g), the relative standard deviation for repeatability (RSDr) ranged from 2.9–23.2%. The relative standard deviation for reproducibility (RSDR) ranged from 20.9–35.3%, and HorRat values of between 1.0 and 1.6 were obtained.

scholarly journals Full validation of curcumin analytical method by LC-MS/MS points out that the degree of hemolysis in plasma affects the quantitation: application in dog plasma study

2019 ◽  
Vol 62 (4) ◽  
Author(s):  
Mariana Dolores ◽  
Alma Villaseñor ◽  
Alma Revilla Vázquez ◽  
Helgi Jung ◽  
Victor Hugo Santiago Rios ◽  
...  
Keyword(s):  
Internal Standard ◽  
Daily Practice ◽  
Reaction Monitoring ◽  
Selective Method ◽  
Clopidogrel Bisulfate ◽  
Dog Plasma ◽  
Relative Standard ◽  
Molecular Reaction ◽  
Acquity Uplc

Abstract. Curcumin has gained great attention in the last decades due to its fascinating properties for humans, such as anti-inflammatory or as cytotoxic against cancer. These effects are also claimed for pets such as cats and dogs, where curcumin administration is a daily practice routine. However, curcumin presents poor oral bioavailability, driving scientists to look for new delivery systems. In the last decades, several analytical methods for the quantification of curcumin in plasma have been published. To our knowledge there are no published reports on the effect of the level of hemolysis in the determination of this compound. In the present paper, a highly specific, sensitive and selective method is presented using Molecular Reaction Monitoring (SRM) using positive ionization (ESI+) mode. Curcumin and clopidogrel bisulfate – used as internal standard (IS) – were separated on an Acquity UPLC BECH Shield RP 18 column (1.7µm, 2.1 X 100mm) with 0.1% formic acid in acetonitrile and water in proportion of 60:40 (v/v). The analyte transitions were 369.3→177.06 m/z for curcumin and 322→212.05 m/z for IS. The method was fully validated and showed good linearity (R2 ≥ 0.999) over the range of 3-160 ng/mL. The Relative Standard Deviation (RSD) were less than 6% for intra-and inter-day analysis and recovery spanned 85-95%. We proved that the degree of hemolysis impaired curcumin quantitation. This method was applied to test curcumin bioavailability in both a mucoadhesive nanocapsule formulation and traditional capsules in dogs that attended routine veterinary consultation.Resumen. La curcumina ha ganado gran atención en las últimas décadas debido a sus propiedades terapéuticas para los humanos, como antiinflamatorio o citotóxico contra el cáncer. Estos efectos también se observan en pequeñas especies como gatos y perros, donde la administración de curcumina se ha vuelto una alternativa. Sin embargo, la curcumina presenta una baja biodisponibilidad oral, lo que impulsa a los científicos a buscar nuevos sistemas de administración. En las últimas décadas, se han publicado varios métodos analíticos para la cuantificación de curcumina en plasma. Actualmente, no hay informes publicados sobre el efecto del grado de hemólisis en la determinación de este compuesto. En este trabajo se desarrolló un método específico, sensible y selectivo utilizando el Monitoreo de reacción seleccionado (SRM) en modo de ionización positiva (ESI +). La curcumina y el bisulfato de clopidogrel, utilizado como patrón interno (IS), se separaron en una columna Acquity UPLC BECH Shield RP 18 (1,7 μm, 2,1 X 100 mm) con ácido fórmico al 0,1% en acetonitrilo y agua a una proporción de 60:40 (v/v). Las transiciones de los analitos fueron 369.3 → 177.06 m/z para curcumina y 322 → 212.05 m/z para IS. El método fue validado y demostró ser lineal (r2 ≥ 0.999) en el rango de 3-160 ng/mL. La desviación relativa estándar (RSD) fue inferior al 6% para el análisis intra e interdía y el porcentaje de recuperación fue 85-95%. Se descubrió que el grado de hemólisis afecta la cuantificación de curcumina. El método desarrollado se aplicó para evaluar la biodisponibilidad de curcumina tanto en una formulación de nanocápsulas mucoadhesivas como en cápsulas tradicionales en perros que asistieron a consultas veterinarias de rutina.

Proton Magnetic Resonance Spectroscopic Method for Determination of Phenylbutazone and Oxyphenbutazone in Tablets

1988 ◽  
Vol 71 (3) ◽  
pp. 525-527
Author(s):  
Sajid Husain ◽  
M Kifayatullah ◽  
R NAGESWARA RAO
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Proton Magnetic Resonance ◽  
Spectroscopic Method ◽  
Internal Standard ◽  
Aromatic Proton ◽  
British Pharmacopoeia ◽  
Standard Deviations ◽  
Proton Resonances

Abstract A simple, specific, and rapid 'H nuclear magnetic resonance spectroscopic method for the assay of phenylbutazone and oxyphenbutazone is described. Spectra are recorded in CDC13 containing 1,3- dichloro-5-nitrobenzene as an internal standard. The aromatic proton resonances for the standard, at 57.7 and 8.2, are well separated from those of phenylbutazone and oxyphenbutazone, which are in the region of 56.5-7.3 ppm. Average percent recoveries of phenylbutazone and oxyphenbutazone were 98.9 and 98.6 with standard deviations of 0.6 and 0.7, respectively. Commercial formulations were analyzed and the results obtained by the proposed method closely agreed with those found by the British Pharmacopoeia method

scholarly journals DEVELOPMENT AND VALIDATION OF UV-VISIBLE SPECTROPHOTOMETRIC METHOD FOR DETERMINATION OF DULOXETINE

2019 ◽  
pp. 27-31
Author(s):  
LIPSA SAMAL ◽  
AMARESH PRUSTY
Keyword(s):  
Spectrophotometric Method ◽  
Spectroscopic Method ◽  
Solvent System ◽  
Spectrophotometric Analysis ◽  
Thiophene Derivative ◽  
Experimental Conditions ◽  
Relative Standard ◽  
Uv Visible ◽  
Development And Validation

Objective: The aim of the present work was to develop and validate a simple UV spectroscopic method for the determination of duloxetine, which is a thiophene derivative and a selective neurotransmitter reuptake inhibitor for serotonin, norepinephrine, and to lesser degree dopamine. Methods: The UV Spectrophotometric analysis was performed using Shimadzu UV-1800 and Shimadzu UV-1700 spectrophotometer by using solvent system acetonitrile and water in the ratio of 8:2. Detection was performed at a wavelength of 290 nm. Method validation was carried out according to ICH Q2R1 guidelines by taking the parameters linearity, accuracy, precision, ruggedness, and robustness, LOD and LOQ. Results: The UV Spectrophotometric method was found linear in the range of 10-50 μg/ml. The method was rugged and robust with % relative standard deviation less than 2. The extraction recoveries were found to be higher than 99% in all experimental conditions. Conclusion: Based upon the performance characteristics, the proposed method was found accurate, precise and rapid and suitable for the determination of Duloxetine for routine analysis.

Comparison of LC-MS/MS and Enzymatic Methods for the Determination of Total Choline and Total Carnitine in Infant Formula and Milk Products

2020 ◽  
Vol 103 (5) ◽  
pp. 1293-1300
Author(s):  
Brendon D Gill ◽  
Harvey E Indyk ◽  
Tadashi Kobayashi ◽  
Iain J McGrail ◽  
David C Woollard
Keyword(s):  
Infant Formula ◽  
Internal Standard ◽  
Standard Technique ◽  
Enzymatic Assays ◽  
Relative Standard ◽  
Fit For Purpose ◽  
Testing Environments ◽  
Total Carnitine ◽  
Release Testing ◽  
Enzymatic Methods

Abstract Background Choline and l-carnitine are classified as pseudo-vitamins because of their conditionally essential status. As they are involved in multiple physiological metabolic pathways in the human body, they are routinely fortified in infant and adult nutritional formulas. Objective The performance of an LC-MS/MS method for the analysis of choline and carnitine, compared with enzymatic methods in routine use for the analysis of total carnitine and total choline, is described. Method Powder samples were reconstituted, with release of carnitine and choline facilitated by both acid and alkaline hydrolysis and the extract analyzed by LC-MS/MS. Quantitation was by internal standard technique using deuterium-labeled carnitine and deuterium-labeled choline. Results Method range, specificity, sensitivity, precision, recovery, accuracy, and ruggedness were assessed for milk powders, infant formulas, and soy- and milk-based nutritional products. Spike recoveries of 94.0–108.4% were obtained for both total carnitine and choline, and no statistical bias (α = 0.05) between measured results and certified values (choline: P = 0.36; free carnitine: P = 0.67) was found for NIST 1849a certified reference material (NIST1849a). Precision, as repeatability relative standard deviation (RSD), was 2.0% RSDr for total carnitine and 1.7% RSDr for total choline. Equivalent results for total choline and total carnitine were obtained by LC-MS/MS and enzymatic methods (n = 30). Conclusions The described LC-MS/MS method is fit for purpose for routine product compliance release testing environments. This validation study has confirmed that alternative enzymatic assays can be used with confidence in laboratories in which LC-MS/MS platforms are unavailable. Highlights An LC-MS/MS method was evaluated and found to be fit-for-purpose for routine product compliance release testing of infant formula. The LC-MS/MS method was compared with enzymatic methods for the analysis of total carnitine and total choline. Alternative enzymatic assays can be used with confidence in laboratories in which LC-MS/MS platforms are unavailable.

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