scholarly journals An HPLC–PDA method for determination of alectinib concentrations in the plasma of an adolescent

2020 ◽  
Vol 32 (3) ◽  
pp. 166-169
Author(s):  
Samiuela Lee ◽  
Christa E. Nath ◽  
Ben W. R. Balzer ◽  
Craig R. Lewis ◽  
Toby N. Trahair ◽  
...  
Keyword(s):  
Formic Acid ◽  
High Performance ◽  
Small Cell Lung ◽  
Linear Calibration ◽  
Lung Cancers ◽  
Anaplastic Lymphoma ◽  
Array Detection ◽  
Alk Positive ◽  
Aqueous Formic Acid

Alectinib is a central nervous system-active small molecule anaplastic lymphoma kinase (ALK) inhibitor that is effective in the treatment of patients with ALK positive tumors, including advanced non-small cell lung cancers and lymphomas. A simple, isocratic high-performance liquid chromatography–photo diode array detection (HPLC–PDA) assay for measurement of alectinib in human plasma is described. Alectinib is extracted from the plasma matrix by addition of methanol, followed by centrifugation and acidification with 0.1% formic acid. It elutes with a run time of 4.6 min using a 250 mm × 4.6 mm RP-C18 column with 0.1% aqueous formic acid and methanol (35:65, v/v) and a flow rate of 1 mL/min. Detection was at 339 nm. Linear calibration plots were achieved in the range of 0.1–20 μg/mL for alectinib (r2 = 0.9996). With limits of detection and quantification of 0.05 and 0.1 μg/mL, respectively, and excellent precision (%CV < 10%), accuracy (bias < ±12%), and recovery (>97%) within the 1–20 μg/mL concentration range, this assay was suitable for measuring pre-dose alectinib concentrations in an adolescent receiving 600-mg doses twice daily.

scholarly journals Simultaneous Determination of 12 Marker Components in Yeonkyopaedok-san Using HPLC–PDA and LC–MS/MS

2020 ◽  
Vol 10 (5) ◽  
pp. 1713 ◽  
Author(s):  
Chang-Seob Seo ◽  
Hyeun-Kyoo Shin
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Formic Acid ◽  
Coefficient Of Determination ◽  
Photodiode Array Detection ◽  
Mobile Phases ◽  
Photodiode Array ◽  
Array Detection ◽  
Aqueous Formic Acid

Yeonkyopaedok-san is a traditional Korean medicine used in the early treatment of boils. In the present study, its 12 marker components for quality control were determined using high-performance liquid chromatography (HPLC) with photodiode array detection and ultra-performance liquid chromatography–mass spectrometry with tandem mass spectrometry (UPLC–MS/MS). The investigated 12 marker components of Yeonkyopaedok-san were as follows: 3-caffeoylquinic acid, cimifugin 7-glucoside, liquiritin apioside, ferulic acid, narirutin, 5-O-methylvisammioside, naringin, neohesperidin, oxypeucedanin hydrate, arctigenin, glycyrrhizic acid, and 6-gingerol. The analytical column used for the separation of the 12 marker analytes in Yeonkyopaedok-san was a Waters SunFire C18 column (4.6 mm × 250 mm, 5 μm). The two mobile phases used were 0.1% (v/v) aqueous formic acid and 0.1% (v/v) formic acid in acetonitrile. In the UPLC–MS/MS analysis, all components were separated using a Waters ACQUITY UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm). The two mobile phases used were 0.1% (v/v) aqueous formic acid and acetonitrile. The coefficient of determination of the calibration curves in both analysis systems showed good linearity (>0.99). The amounts of the 12 marker components in Yeonkyopaedok-san determined using HPLC–photodiode array detection and UPLC–MS/MS analyses were found to be 0.14–9.00 mg/g and 2.35–853.11 μg/g, respectively.

scholarly journals Patterns of Metastatic Spread and Mechanisms of Resistance to Crizotinib in ROS1-Positive Non–Small-Cell Lung Cancer

2017 ◽  
pp. 1-13 ◽  
Author(s):  
Justin F. Gainor ◽  
Diane Tseng ◽  
Satoshi Yoda ◽  
Ibiayi Dagogo-Jack ◽  
Luc Friboulet ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Molecular Mechanisms ◽  
Small Cell ◽  
Metastatic Spread ◽  
Imaging Data ◽  
Resistance Mutations ◽  
Small Cell Lung ◽  
Lung Cancers ◽  
Anaplastic Lymphoma ◽  
Alk Positive

Purpose The ROS1 tyrosine kinase is activated through ROS1 gene rearrangements in 1% to 2% of non–small-cell lung cancers (NSCLCs), which confer sensitivity to treatment with the anaplastic lymphoma kinase (ALK)/ROS1/mesenchymal-epithelial transition factor inhibitor crizotinib. Currently, insights into patterns of metastatic spread and mechanisms of crizotinib resistance among patients with ROS1-positive disease are limited. Patients and Methods We reviewed clinical and radiographic imaging data of patients with ROS1- and ALK-positive NSCLC to compare patterns of metastatic spread at initial metastatic diagnosis. To determine molecular mechanisms of crizotinib resistance, we analyzed repeat biopsy specimens from a cohort of patients with ROS1-positive disease who progressed on crizotinib. Results We identified 39 and 196 patients with advanced ROS1- and ALK-positive NSCLC, respectively. Patients with ROS1-positive disease had significantly lower rates of extrathoracic metastases ( ROS1, 59.0%; ALK, 83.2%; P = .002), including lower rates of brain metastases ( ROS1, 19.4%; ALK, 39.1%; P = .033), at initial metastatic diagnosis. Despite similar overall survival between patients with ALK- and ROS1-positive NSCLC treated with crizotinib (median, 3.0 v 2.5 years, respectively; P = .786), patients with ROS1-positive NSCLC also had a significantly lower cumulative incidence of brain metastases (34% v 73% at 5 years; P < .001). In addition, we identified 16 patients who underwent a total of 17 repeat biopsies after progression on crizotinib. ROS1 resistance mutations were identified in 53% of specimens, including nine (64%) of 14 non–brain metastasis specimens. ROS1 mutations included G2032R (41%), D2033N (6%), and S1986F (6%). Conclusion Compared with ALK rearrangements, ROS1 rearrangements are associated with lower rates of extrathoracic metastases, including fewer brain metastases, at initial metastatic diagnosis. ROS1 resistance mutations, particularly G2032R, appear to be the predominant mechanism of resistance to crizotinib, which underscores the need to develop novel ROS1 inhibitors with activity against these resistant mutants.

scholarly journals Feasibility Study for the Production of Certified Calibrants for the Determination of Deoxynivalenol and Other B-Trichothecenes: Intercomparison Study

2006 ◽  
Vol 89 (6) ◽  
pp. 1573-1580 ◽  
Author(s):  
Rudolf Krska ◽  
Elvira Welzig ◽  
Elisabeth Drs ◽  
Ralf D Josephs ◽  
Ronald C Schothorst ◽  
...  
Keyword(s):  
High Performance ◽  
Certified Reference Materials ◽  
Electron Capture Detection ◽  
Linear Calibration ◽  
Target Value ◽  
Funded Project ◽  
Array Detection ◽  
The Common ◽  
Intercomparison Study

Abstract Thirteen European laboratories experienced in the analysis of mycotoxins participated in an intercomparison study within a European Commission-funded project. Goals of the study were to check the fitness for purpose of a small batch of gravimetrically prepared calibrants; to compare individually prepared calibrants with common calibrants; to check the feasibility of toxin mixtures as calibrant solutions; and to give recommendations on the production of future certified reference materials (CRMs) with regard to the nature of the calibrant and the means of certification. Each laboratory received ampules of each common calibrant containing single toxins [solution containing either deoxynivalenol (DON), 3-acetyl-DON (3-Ac-DON), nivalenol (NIV), or 15-acetyl-DON (15-Ac-DON)] and 3 ampules of toxinmixture (solutions of DON 3-Ac-DON NIV in acetonitrile) of known concentrations (about 20 g/mL). Ampules with single toxins (solution containing either DON, 3-Ac-DON, NIV, or 15-Ac-DON) and a toxinmixture (solutions of DON 3-Ac-DON NIV in acetonitrile) of unknown concentrations were distributed to the participants for quantification. The participating laboratories used mainly high-performance liquid chromatography (HPLC)diode array detection UV for DON, 3-Ac-DON, NIV, and 15-Ac-DON; gas chromatography-electron capture detection (GC-ECD) and GC-mass spectrometry methods were used sparingly. Linear calibration curves were achieved by &gt;90% of the participants. Relative between-day variation (RSDr) of 26% of the laboratories was greater than the target value of 5% for HPLC, and RSDr of 32% of the laboratories was greater than the desired value of 10% for GC. Relative between-laboratory variation (RSDR) of the GC results obtained with single common calibrants was greater than the target value of 16% for all laboratories. RSDR of the HPLC results for the common unknown single toxin solutions was less than the target value of 8% except for 15-Ac-DON. Generally, better recoveries were observed from common calibrants (102% for mix calibrants and 98% for single calibrants) than from individually prepared calibrants (95%). This international comparison study clearly showed the high scattering of results in the analysis of type-B trichothecenes, particularly when GC was used. Obviously, this intercomparison study was not suited for the certification of B-trichothecenes. A certification of the proposed calibrant material was therefore recommended on the basis of its gravimetrical preparation.

Separation and Determination of Some Aromatic Sulfones by Reversed-Phase High-Performance Liquid Chromatography

1994 ◽  
Vol 59 (3) ◽  
pp. 569-574 ◽  
Author(s):  
Josef Královský ◽  
Marta Kalhousová ◽  
Petr Šlosar
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Mobile Phase ◽  
High Performance ◽  
Reversed Phase ◽  
Uv Spectra ◽  
Optimum Conditions ◽  
Linear Calibration ◽  
Technical Grade

The reversed-phase high-performance liquid chromatography of some selected, industrially important aromatic sulfones has been investigated. The chromatographic behaviour of three groups of aromatic sulfones has been studied. The optimum conditions of separation and UV spectra of the sulfones and some of their hydroxy and benzyloxy derivatives are presented. The dependences of capacity factors vs methanol content in mobile phase are mentioned. The results obtained have been applied to the quantitative analysis of different technical-grade samples and isomer mixtures. For all the separation methods mentioned the concentration ranges of linear calibration curves have been determined.

scholarly journals Determination of 19 Psychoactive Substances in Premortem and Postmortem Whole Blood Samples Using Ultra-High-Performance Liquid Chromatography–Tandem Mass Spectrometry

Separations ◽  
2021 ◽  
Vol 8 (6) ◽  
pp. 78
Author(s):  
Sevasti Karampela ◽  
Jessica Smith ◽  
Irene Panderi
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Formic Acid ◽  
Whole Blood ◽  
High Performance ◽  
Tandem Mass ◽  
Psychoactive Substances ◽  
Blood Samples ◽  
Whole Blood Samples

An ever-increasing need exists within the forensic laboratories to develop analytical processes for the qualitative and quantitative determination of a broad spectrum of new psychoactive substances. Phenylethylamine derivatives are among the major classes of psychoactive substances available on the global market and include both amphetamine analogues and synthetic cathinones. In this work, an ultra-high-performance liquid chromatography-positive ion electrospray ionization tandem mass spectrometric method (UHPLC-ESI-MS/MS) has been developed and fully validated for the determination of 19 psychoactive substances, including nine amphetamine-type stimulants and 10 synthetic cathinone derivatives, in premortem and postmortem whole blood. The assay was based on the use of 1 mL premortem or postmortem whole blood, following solid phase extraction prior to the analysis. The separation was achieved on a Poroshell 120 EC-C18 analytical column with a gradient mobile phase of 0.1% formic acid in acetonitrile and 0.1% formic acid in water in 9 min. The dynamic multiple reaction monitoring used in this work allowed for limit of detection (LOD) and lower limit of quantitation (LOQ) values of 0.5 and 2 ng mL−1, respectively, for all analytes both in premortem and postmortem whole blood samples. A quadratic calibration model was used for the 12 quantitative analytes over the concentration range of 20–2000 ng mL−1, and the method was shown to be precise and accurate both in premortem and postmortem whole blood. The method was applied to the analysis of real cases and proved to be a valuable tool in forensic and clinical toxicology.

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