Validated Chiral LC-ESI-MS/MS Method for the Simultaneous Quantification of Darolutamide Diastereomers and Its Active Metabolite in Mice Plasma: Application to a Pharmacokinetic Study

Drug Research ◽  
2018 ◽  
Vol 68 (11) ◽  
pp. 615-624
Author(s):  
Narayan Balaji ◽  
Suresh Sulochana ◽  
Neeraj Saini ◽  
Siva A. ◽  
Ramesh Mullangi
Keyword(s):  
Pharmacokinetic Study ◽  
Active Metabolite ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Triple Quadrupole Mass Spectrometer ◽  
Liquid Liquid Extraction ◽  
Regulatory Guidelines ◽  
Negative Ionization Mode ◽  
Ionization Mode ◽  
Negative Ionization

AbstractA simple, selective and reliable LC-MS/MS method was developed and validated for the simultaneous quantitation of darolutamide diastereomers (diastereomer-1 and diastereomer-2) and its active metabolite i. e. ORM-15341 in mice plasma using warfarin as an internal standard (IS) as per the regulatory guidelines. Plasma samples were extracted by liquid-liquid extraction and the chromatographic separation was achieved on a Chiralpak IA column with an isocratic mobile phase 5 mM ammonium acetate:absolute alcohol (20:80, v/v) at a flow rate of 1.0 mL/min. Detection and quantitation was done by multiple reaction monitoring on a triple quadrupole mass spectrometer following the transitions: m/z 397→202, 395→202 and 307→250 for darolutamide diastereomers, ORM-15341 and the IS, respectively in the negative ionization mode. The calibration curves were linear (r>0.992) in the range of 100–2400 ng/mL for all the analytes. The intra- and inter-day precisions were in the range of 1.25–10.2 and 1.58-12.3; 2.85-5.68 and 1.85-9.58; 2.34-12.1 and 2.58-7.38 for diastereomer-1, diastereomer-2 and ORM-15341, respectively. Both diastereomers and ORM-15341 were found to be stable under different stability conditions. The validated method was applied to a pharmacokinetic study in mice.

scholarly journals UHPLC-QQQ-MS/MS assay for the quantification of dianthrones as potential toxic markers of Polygonum multiflorum Thunb: applications for the standardization of traditional Chinese medicines (TCMs) with endogenous toxicity

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jian-Bo Yang ◽  
Yun-Fei Song ◽  
Yue Liu ◽  
Hui-Yu Gao ◽  
Qi Wang ◽  
...  
Keyword(s):  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Triple Quadrupole ◽  
Quadrupole Mass ◽  
Polygonum Multiflorum ◽  
Triple Quadrupole Mass Spectrometer ◽  
Heparg Cells ◽  
Negative Ionization Mode ◽  
Negative Ionization

Abstract Background The raw and processed roots of Polygonum multiflorum Thunb (PM) are commonly used in clinical practice to treat diverse diseases; however, reports of hepatotoxicity induced by Polygoni Multiflori Radix (PMR) and Polygoni Multiflori Radix Praeparata (PMRP) have emerged worldwide. Thus, it is necessary for researchers to explore methods to improve quality standards to ensure their quality and treatment effects. Methods In the present study, an ultra-high performance liquid chromatography triple quadrupole mass spectrometry (UHPLC-QQQ-MS/MS) method was optimized and validated for the determination of dianthrones in PMR and PMRP using bianthronyl as the internal standard. Chromatographic separation with a gradient mobile phase [A: acetonitrile and B: water containing 0.1% formic acid (v/v)] at a flow rate of 0.25 mL/min was achieved on an Agilent ZORBAX SB-C18 column (2.1 mm × 50 mm, 1.8 μm). The triple quadrupole mass spectrometer (TQMS) was operated in negative ionization mode with multiple reaction monitoring for the quantitative analysis of six dianthrones. Moreover, compounds 5 and 6 were further evaluated for their cytotoxicity in HepaRG cells by CCK-8 assay. Results The UHPLC-QQQ-MS/MS method was first developed to simultaneously determine six dianthrones in PMR and PMRP, namely, polygonumnolides C1–C4 (1–4), trans-emodin dianthrones (5), and cis-emodin dianthrones (6). The contents of 1–6 in 90 batches of PMR were in the ranges of 0.027–19.04, 0.022–13.86, 0.073–15.53, 0.034–23.35, 0.38–83.67 and 0.29–67.00 µg/g, respectively. The contents of 1–6 in 86 batches of commercial PMRP were in the ranges of 0.020–13.03, 0.051–8.94, 0.022–7.23, 0.030–12.75, 0.098–28.54 and 0.14–27.79 µg/g, respectively. Compounds 1–4 were almost completely eliminated after reasonable processing for 24 h and the contents of compounds 5 and 6 significantly decreased. Additionally, compounds 5 and 6 showed inhibitory activity in HepaRG cells with IC50 values of 10.98 and 15.45 μM, respectively. Furthermore, a systematic five-step strategy to standardize TCMs with endogenous toxicity was proposed for the first time, which involved the establishment of determination methods, the identification of potentially toxic markers, the standardization of processing methods, the development of limit standards and a risk–benefit assessment. Conclusion The results of the cytotoxicity evaluation of the dianthrones indicated that trans-emodin dianthrones (5) and cis-emodin dianthrones (6) could be selected as toxic markers of PMRP. Taking PMR and PMRP as examples, we hope this study provides insight into the standardization and internationalization of endogenous toxic TCMs, with the main purpose of improving public health by scientifically using TCMs to treat diverse complex diseases in the future.

scholarly journals Quantification of Nineteen Bioactive Components in the Ancient Classical Chinese Medicine Formula of Wen-Dan Decoction and Its Commercial Preparations by UHPLC-QQQ-MS/MS

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2031 ◽  
Author(s):  
Bing Zhang ◽  
Dongli Qi ◽  
Xiuping Deng ◽  
Zhe Ma ◽  
Yumei Wu ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Multiple Reaction Monitoring ◽  
Principal Component ◽  
Hierarchical Cluster ◽  
Gradient Elution ◽  
Triple Quadrupole Mass Spectrometer ◽  
Ionization Mode ◽  
Negative Ionization ◽  
High Concentrations ◽  
Acquity Uplc

A UHPLC-QQQ-MS/MS method was developed to quantify the significant constituents in Wen-Dan Decoction (WDD), a traditional Chinese medicine. Analysis of 19 compounds was conducted on an ACQUITY UPLC® BEH C18 Column (2.1 × 50 mm, 1.7 μm) using elution with a gradient elution of acetonitrile and 0.05% (v/v) formic acid in water. A triple quadrupole mass spectrometer was operated in negative ionization mode and positive ionization mode by multiple reaction monitoring (MRM), respectively. All calibration curves showed acceptable linearity (r ≥ 0.9950). The RSDs of intra- and inter-day precisions of low, mid and high concentrations were ≤ 8.88%. The repeatabilities (RSDs ≤ 7.17%) and stabilities (RSD ≤ 4.79%) of the samples were qualified. The recoveries were found in the range of 93.07 ± 3.86 to 103.98 ± 2.98% with the RSD varying between 1.30 and 7.86%. The final rapid, sensitive, precise, accurate and reliable UHPLC-QQQ-MS/MS method was used for the simultaneous quantification of 19 constituents in WDD and its commercial preparations. The strategy of combining the contents of the 19 chemicals in a daily dose of the WDD preparations with the hierarchical cluster analysis and the 3D principal component analysis was employed to effectively distinguish the WDD preparations provided by the different suppliers, which represents a contribution to the evaluation and control of the quality of WDD (or other decoctions consisting of the same herbs) and the preparations of WDD in other dosage forms such as tablets and granules.

Sensitive LC-MS/MS Method for the Simultaneous Determination of Bendamustine and its Active Metabolite, γ-Hydroxybendamustine in Small Volume Mice and Dog Plasma and its Application to a Pharmacokinetic Study in Mice and Dogs

Drug Research ◽  
2017 ◽  
Vol 67 (09) ◽  
pp. 497-508 ◽  
Author(s):  
Devaraj Chandrashekar ◽  
Ponnayyan Suresh ◽  
Rajnish Kumar ◽  
Ravi Bhamidipati ◽  
Ramesh Mullangi ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Small Volume ◽  
Internal Standard ◽  
Simultaneous Quantification ◽  
Liquid Liquid Extraction ◽  
Dog Plasma ◽  
Highly Sensitive ◽  
Regulatory Guidelines ◽  
Novel Method

AbstractA highly sensitive, specific and rapid LC-ESI-MS/MS method has been developed and validated for the simultaneous quantification of bendamustine (BM) and γ-hydroxybendamustine (HBM) in small volume (20 µL) mice and dog plasma using phenacetin as an internal standard (IS) as per regulatory guidelines. Both the analytes and IS were extracted from mice and dog plasma using a liquid-liquid extraction method. Chromatography was achieved on Atlantis dC18 column using an isocratic mobile phase (0.2% formic acid:acetonitrile, 25:75) at a flow rate of 0.40 mL/min. The total chromatographic run time was 3.0 min and the elution of BM, HBM and IS occurred at ~1.2, 1.2 and 2.0 min, respectively. A linear response function was established 0.11–518 ng/mL for both the analytes in mice and dog plasma. The intra- and inter-day accuracy and precisions were in the range of 3.46–12.9 and 3.63–8.23%; 1.15–9.00 and 7.86–9.49% for BM and HBM, respectively in mice plasma and 2.15–6.49 and 1.73–13.1%; 4.35–13.9 and 4.33–10.5% for BM and HBM, respectively in dog plasma. This novel method has been applied to a pharmacokinetic study in mice and dogs.

Simultaneous Determination of 44 Pesticides in Tobacco by UPLC/MS/MS and a Modified QuEChERS Procedure

2013 ◽  
Vol 96 (2) ◽  
pp. 422-431 ◽  
Author(s):  
Xuyan Chen ◽  
Kongxiang Zhao ◽  
Baokun Ge ◽  
Qiyong Chen
Keyword(s):  
Multiple Reaction Monitoring ◽  
Graphitized Carbon Black ◽  
Modified Quechers ◽  
Negative Ionization Mode ◽  
Multiple Reaction Monitoring Mode ◽  
Primary Secondary Amine ◽  
Standard Calibration ◽  
Ionization Mode ◽  
Negative Ionization

Abstract A novel, simple, and rapid method for determination of the residues of 44 commonly used pesticides in tobacco was developed based on modified Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) procedures. The pesticides were extracted with acetonitrile and purified on a mixed sorbents column of primary secondary amine, C18, and graphitized carbon black. Quantitative determination of all pesticides was performed by ultra-performance LC/MS/MS in the positive or negative ionization mode by a single run due to the fast polarity switching capability of the mass spectrometer. Two precursor-product ion transitions were monitored for each compound in the multiple reaction monitoring mode. Quantification was carried out using matrix-matched standard calibration. The method has been validated by various tobacco cultivars, such as Burley, Oriental, and Virginia from different countries. Recoveries of the proposed method for spiked samples ranged from 71.1 to 109.8%, and RSD values were below 10%. The LOQ values were are all below the guidance residue levels proposed by the Agrochemical Advisory Committee of Cooperation Center for Scientific Research Relative to Tobacco. This method is valuable for measurement of pesticide residues in tobacco for QC and monitoring.

scholarly journals Development and Validation of an LC-MS/MS Assay to Quantitate 2′,4′,6′-Trihydroxyacetophenone in Rat and Dog Plasma and its Application to a Pharmacokinetic Study

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4373
Author(s):  
Hee Jo Yoo ◽  
Se-Jung Hwang ◽  
Jeong-Hun Lee ◽  
Wang-Seob Shim ◽  
Yun-Woong Choi ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Ammonium Acetate ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Dog Plasma ◽  
Limit Of Quantitation ◽  
Regulatory Guidelines ◽  
One Step ◽  
Standard Calibration ◽  
Development And Validation

In the present study, a simple, rapid, and reliable bioanalytical method was developed using liquid chromatography with tandem-mass spectrometry (LC-MS/MS) to quantify 2′,4′,6′-trihydroxyacetophenone (THAP) in rat and dog plasma with 2′,4′,6′-trihydroxybenzaldehyde as an internal standard (IS). The LC-MS/MS instrument was operated in the multiple reaction monitoring (MRM) mode to detect THAP at m/z transition 166.89 > 82.8 and IS at 152.89 > 82.8, respectively. A simple, one-step protein precipitation (PP) method was employed with acetonitrile for sample preparation. Utilizing a Gemini C18 column, THAP and IS were separated with an isocratic mobile phase consisting of 10 mM ammonium acetate and methanol (10:90, v/v) at a flow rate of 0.2 mL/min. Total chromatographic run time was 2.5 min per sample injection. The standard calibration curve for THAP was linear (r2 ≥ 0.9987) over the concentration range of 0.1 to 100 µg/mL with the lower limit of quantitation (LLOQ) of 0.1 µg/mL (S/N ratio > 10). According to the regulatory guidelines from the U.S. Food and Drug Administration (FDA) and the Korea Ministry of Food and Drug Safety (MFDS), our newly developed biomedical analytical method was fully and adequately validated in terms of selectivity, sensitivity, linearity, intra- and inter-day precision and accuracy, recovery, matrix effect, stability, and dilution integrity. Our validated assay was successfully utilized in a nonclinical pharmacokinetic study of THAP in rats and dogs.

scholarly journals UPLC-MS/MS Method for the Determination of 14 Compounds in Rat Plasma and Its Application in a Pharmacokinetic Study of Orally Administered Xiaoyao Powder

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2514 ◽  
Author(s):  
Mingyue Xu ◽  
Zhanling Xu ◽  
Qingxuan Xu ◽  
Hongyue Zhang ◽  
Mingyang Liu ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Chinese Herbs ◽  
Tandem Mass ◽  
Ionization Source ◽  
Liquid Chromatography Tandem Mass ◽  
Negative Ionization

Xiaoyao Powder (XYP), a common Chinese medicine, comprises eight traditional Chinese herbs and has been widely used clinically to treat liver damage and mental disorders. An ultra-performance liquid chromatography–tandem mass spectrometry method was developed to investigate the pharmacokinetics of 14 compounds (albiflorin, paeoniflorin, ferulic acid, senkyunolide I, quercetin, isoliquiritigenin, atractylenolide III, ligustilide, atractylenolide II, liquiritin, liquiritigenin, saikosaponin c, glycyrrhizic acid, and saikosaponin a) in XYP. Naringenin was used as the internal standard. The compounds were separated using an ACQUITY UPLCTM BEH C18 column (1.7 μm, 50 × 2.1 mm) with a mobile phase consisting of acetonitrile and 0.1% formic acid in water at a flow rate of 0.3 mL/min. Detection was performed on a triple-quadrupole tandem mass spectrometer using multiple reaction monitoring and an electrospray ionization source in both positive and negative ionization modes. All calibration curves exhibited good linearity (r2 > 0.9974) over the measured ranges. The intra- and inter-day precisions were within 12%, and the accuracy ranged from 89.93% to 106.64%. Extraction recovery and matrix effect results were satisfactory. The method was successfully applied in a pharmacokinetic study of the 14 compounds in rat plasma after the oral administration of XYP.

scholarly journals Determination of Anlotinib, a Tyrosine Kinase Inhibitor, in Rat Plasma by UHPLC-MS/MS and Its Application to a Pharmacokinetic Study

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Zhe Wang ◽  
Le-jing Lian ◽  
Yan-yan Dong ◽  
Xiao Cui ◽  
Jian-chang Qian ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Kinase Inhibitor ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Rat Plasma ◽  
Reaction Monitoring ◽  
Receptor Kinase ◽  
Quadrupole Mass ◽  
Triple Quadrupole Mass Spectrometer

Anlotinib is a novel inhibitor of receptor kinase tyrosine with multitargets and has a broad spectrum of inhibitory action on tumor angiogenesis and growth. A simple and rapid UHPLC-MS/MS bioanalytical method was validated for the determination of anlotinib in rat plasma, using imatinib as an internal standard. An Acquity BEH C18 column was used to separate analytes. The eluents consisted of formic acid/water (0.1 : 100, v/v) and acetonitrile with a mobile phase. A triple quadrupole mass spectrometer was operated for the quantification with multiple reaction monitoring (MRM) to determine transitions: 408.2 ⟶ 339.1 for anlotinib, and 494.3 ⟶ 394.1 for imatinib. The validated range was 0.1–50 ng/mL for anlotinib. Mean recovery rate of anlotinib in plasma was ≥99.32% and reproducible. Also, the intra- and interday precisions were both below 15%. This robust method was successfully applied to support the pharmacokinetic study of anlotinib in rats.

A Validated LC–MS/MS Method for Simultaneous Determination of 3-O-Acetyl-11-Keto-β-Boswellic Acid (AKBA) and its Active Metabolite Acetyl-11-Hydroxy-β-Boswellic Acid (Ac-11-OH-BA) in Rat Plasma: Application to a Pharmacokinetic Study

2020 ◽  
Vol 58 (6) ◽  
pp. 485-493
Author(s):  
Tarun Sharma ◽  
Snehasis Jana
Keyword(s):  
Simultaneous Determination ◽  
Pharmacokinetic Study ◽  
Active Metabolite ◽  
Dynamic Range ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Rat Plasma ◽  
Boswellic Acid ◽  
Mass Detection

Abstract The aim of this study was to develop and validate a new, rapid, sensitive, selective and reliable liquid chromatography–tandem mass spectrometry method for simultaneous determination of 3-O-Acetyl-11-keto-β-boswellic acid (AKBA) and its active metabolite 3-O-Acetyl-11-hydroxy-β-boswellic acid (Ac-11-hydroxy-BA) in rat plasma. Both analytes (AKBA and Ac-11-hydroxy-BA) and the internal standard (IS, ursolic acid) were extracted from 100 μL of rat plasma by protein precipitation. Chromatographic separation was achieved on PRP-H1 RP-C18 column (75 mm × 2 mm, 1.6 μm) using acetonitrile–water (95.5 v/v) as the mobile phase. Mass detection was conducted by electrospray ionization in positive ion multiple reaction monitoring (MRM) mode. A linear dynamic range of 1–1,000 ng/mL for both AKBA and Ac-11-hydroxy-BA was established with mean correlation coefficient (r (1)) of 0.999. Intra- and inter-day precision (% CV) of analysis were found in the range of 1.9–7.4%. The accuracy determined for these analytes ranged from 92.4 to 107.2%. The extraction recoveries for both analytes ranged from 92.6 to 97.3% for spiked plasma samples and were consistent. The % change in stability samples compared to nominal concentration ranged from 0.4 to 4.2%. This method was successfully tested to a pharmacokinetic (PK) study for estimation of AKBA and acetyl-11-hydroxy-BA in rat plasma following oral administration of AKBA. This method has been validated with the advantage of shorter run time that can be used for high-throughput analysis and has been successfully applied to the pharmacokinetic study of AKBA in rats.

scholarly journals IDENTIFIKASI PEWARNA MERAH K3 (CI 15585) DALAM PRODUK KOSMETIK SEDIAAN PERONA MATA SECARA LC- MS/MS

2017 ◽  
Vol 5 (1) ◽  
pp. 34
Author(s):  
Riana Suastari Rahayu ◽  
Iryanti Eka Suprihatin ◽  
Wiwik Susanah Rita
Keyword(s):  
Multiple Reaction Monitoring ◽  
Reaction Monitoring ◽  
Ionization Technique ◽  
Identification Process ◽  
Low Concentrations ◽  
Negative Ionization Mode ◽  
Product Ions ◽  
Ionization Mode ◽  
Negative Ionization ◽  
Red Dye

ABSTRAK : Identifikasi merah K3 dalam sediaan perona mata secara LC-MS/MS dilakukan untuk mengkonfirmasi keberadaannya yang sering kali ditemukan dalam konsentrasi kecil. Metode spektrofotometeri UV-VIS dan HPLC tidak cukup untuk mengkonfirmasi keberadaan merah K3 yang dinyatakan positif dengan metode KLT. Optimasi metode dilakukan pada kondisi spektrometer massa dan sistem kromatografi cair yang berlaku pada LC-MS/MS sebelum dilakukan proses identifikasi. Hasil optimasi menunjukkan identifikasi merah K3 dengan LC-MS/MS menggunakan teknik ionisasi elektrospray (ESI) dan sistem Multiple Reaction Monitoring (MRM) pada mode ionisasi negatif. Ion prekursor pada m/z 375 dan ion produk pada m/z 204, 80, 140 digunakan untuk identifikasi.   ABSTRACT : Identification of red dye (CI 15585) using LC-MS/MS in eye shadow was performed to confirm its presence in very low concentrations. The UV-VIS spectrophotometry and HPLC are not sufficient to confirm the presence of red dye identified by the TLC. The optimation of the method was carried out under the condition applicable to LC-MS / MS prior to identification process. Optimation results show that red dye can be identified with LC-MS/MS using electrospray ionization technique (ESI) and Multiple Reaction Monitoring (MRM) system under negative ionization mode. The precursor ion at m / z 375 and the product ions at m / z 204, 80, 140 are used for identification.      

scholarly journals Simultaneous Determination of 13 Constituents of Radix Polygoni Multiflori in Rat Plasma and Its Application in a Pharmacokinetic Study

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Wenhao Cheng ◽  
Yinghui Li ◽  
Wei Yang ◽  
Siyang Wu ◽  
Mengmeng Wei ◽  
...  
Keyword(s):  
Simultaneous Determination ◽  
Pharmacokinetic Study ◽  
Matrix Effects ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Limit Of Quantitation ◽  
Negative Ionization Mode ◽  
Negative Ionization

Radix Polygoni Multiflori (RPM) has been widely used to treat various diseases in Asian countries for many centuries. Although, stilbenes and anthraquinones, two major components of RPM, show various bioactive effects, it has been speculated that the idiosyncratic hepatotoxicity induced by RPM may be related to these constituents. However, information on the pharmacokinetics of stilbenes and anthraquinones at a subtoxic dose of RPM is limited. A simple and sensitive UPLC-MS/MS bioanalytical method for the simultaneous determination of 13 ingredients of RPM, including chrysophanol, emodin, aloe-emodin, rhein, physcion, questin, citreorosein, questinol, 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside, torachrysone-8-O-glucoside, chrysophanol-8-O-β-D-glucoside, emodin-8-O-β-D-glucoside, and physcion-8-O-β-D-glucoside, in rat plasma was established. Acetonitrile was employed to precipitate the plasma with appropriate sensitivity and acceptable matrix effects. Chromatographic separation was performed using a waters HSS C18 column with a gradient elution using water and acetonitrile both containing 0.025% formic acid within a run time of 9 min. The constituents were detected in negative ionization mode using multiple reaction monitoring. The method was fully validated in terms of selectivity, linearity, accuracy, precision, recovery, matrix effects, and stability. The lower limit of quantitation of the analytes was 0.1–1 ng/mL. The intrabatch and interbatch accuracies were 87.1–109%, and the precision was within the acceptable limits. The method was applied to a pharmacokinetic study after oral administration of RPM extract to rats at a subtoxic dose of 36 g/kg.

Sign in / Sign up

Export Citation Format

Share Document