scholarly journals Analysis for Alpha-Pyrrolidinovalerophenone and Its 2-Oxo-PVP Metabolite in Plasma by Liquid Chromatography–Tandem Mass Spectrometry

2019 ◽  
Author(s):  
David M Andrenyak ◽  
David E Moody ◽  
Jonathan M Crites ◽  
Michael H Baumann
Keyword(s):  
Room Temperature ◽  
Rat Plasma ◽  
Sample Volume ◽  
Internal Standards ◽  
Accuracy And Precision ◽  
Assay Performance ◽  
Liquid Chromatography Tandem Mass ◽  
Assay Precision ◽  
Recreational Use ◽  
Positive Ion

Abstract Alpha-pyrrolidinovalerophenone (alpha-PVP), a novel psychoactive substance, has widespread recreational use. This with interest in its pharmacological effects creates a need for methods that measure alpha-PVP concentrations. We therefore developed a LC-MS/MS method that can quantitate alpha-PVP and 2-oxo-PVP in rat plasma using a 0.1-mL sample volume. Addition of internal standards (2.5 ng/mL alpha-PVP-d8/2-oxo-PVP-d6) was followed by liquid–liquid extraction with 1-chlorobutane:acetonitrile (4:1), evaporation and reconstitution with 0.1% formic acid. Extracts were analyzed by LC-MS/MS using an Agilent 1100 HPLC and a Thermo Scientific TSQ Quantum Access MS/MS, with a YMC ODS-AQ, 50 mm × 2 mm, 3 μm column. The mobile phase was 0.1% formic acid:acetonitrile gradient at a 0.2-mL/minute flow rate with positive ion electrospray. SRM was used for the analysis with transitions: alpha-PVP, 232 → 91; alpha-PVP-d8, 240 → 91; 2-oxo-PVP, 246 → 91; 2-oxo-PVP-d6, 252 → 91. Alpha-PVP and 2-oxo-PVP eluted at 6.4 and 8.9 min. Calibrators range from 0.25 to 500 ng/mL. Accuracy and precision evaluated quality control samples prepared at 0.75, 10 and 400 ng/mL. The intra-assay evaluation also included the 0.25-ng/mL LOQs prepared in six different blank plasma sources. The intra-assay accuracy ranged from 88.9 to 117.8% of the target, and the intra-assay precision ranged from 0.9 to 16.0%. The inter-assay accuracy ranged from 98.7 to 110.7% of the target, and the inter-assay precision ranged from 4.5 to 12.0%. Extraction recovery was at least 52% for alpha-PVP and 67% for 2-oxo-PVP. Ionization recoveries were at least 64% for alpha-PVP and 82% for 2-oxo-PVP. These losses did not adversely affect assay performance. Alpha-PVP and 2-oxo-PVP controls were stable at room temperature for up to 24 h and frozen for at least 36 days. Alpha-PVP and 2-oxo-PVP were also stable in processed samples (extracts) stored at room temperature for at least 24 days. The procedure was used to analyze rat plasma samples from a pharmacokinetic study.

scholarly journals Simultaneous LC-MS/MS Determination of Sacubitril, Valsartan and LBQ657 in Human Plasma and Its Application to Clinical Study

2021 ◽  
Author(s):  
Yufeng Ni ◽  
Yujia Zhang ◽  
Chong Zou ◽  
Li Ding
Keyword(s):  
Human Plasma ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Ionization Source ◽  
Internal Standards ◽  
Accuracy And Precision ◽  
Liquid Chromatography Tandem Mass ◽  
Multiple Reaction Monitoring Mode ◽  
Positive Ion

A rapid and reproducible liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine sacubitril, valsartan and a metabolite of sacubitril (LBQ657) in human plasma using sacubitril-d4 and valsartan-d3 as the internal standards. Following protein precipitation, the analytes were operated on an Ultimate® XB-C18 column (2.1 × 50 mm, 3.5 μm, Welch) with a gradient elution with acetonitrile, and 5 mM ammonium acetate and 0.1% formic acid in water as the mobile phase. The detection was performed on a Triple Quad™ 4000 mass spectrometer coupled with an electrospray ionization source (ESI) under positive-ion multiple reaction monitoring mode. The linearities are 2.00-4000, 5.00-10000 and 5.00-10000 ng mL-1 for sacubitril, valsartan and LBQ657, respectively. The accuracy and precision of intra- and inter-day, dilution accuracy, recovery and stability of the method were all within the acceptable limits and no matrix effect or carryover was observed. The suitability of the method was successfully demonstrated in terms of the quantification of sacubitril, valsartan and LBQ657 in plasma samples collected from healthy Chinese volunteers in a clinical trial.

scholarly journals Determination of Matrine in Rat Plasma after Oral Administration of Novel Korean Herbal Medicine KIOM-MA128 and Application of PK

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Hyun-moon Back ◽  
Byungjeong Song ◽  
Jung-woo Chae ◽  
Hwi-yeol Yun ◽  
Jin Yeul Ma ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Oral Administration ◽  
High Performance ◽  
Rat Plasma ◽  
Pharmacokinetic Studies ◽  
Chemical Marker ◽  
Chromatography Tandem Mass Spectrometry ◽  
Accuracy And Precision ◽  
Liquid Chromatography Tandem Mass

KIOM-MA128 is a novel Korean herbal medicine with antiatopic, anti-inflammatory, and antiasthmatic effects. Matrine is thought to be a potential chemical marker of KIOM-MA128, but pharmacokinetic studies on KIOM-MA128 had not been performed. This study describes a simple and rapid method using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to determine the concentration of matrine in rats plasma after administration of KIOM-MA128. The isocratic mobile phase consisted of methanol and distilled water, and the flow rate was 0.15 mL/min. The accuracy and precision of the assay, as well as stability tests, were performed in accordance with FDA regulations for the validation of bioanalytical methods. The half-life andTmaxof matrine after administration of KIOM-MA128 were 4.29 ± 2.20 h and 1.8 ± 1.23 h, respectively.CmaxandAUCinfof matrine after administration of KIOM-MA128 at 4 g/kg and 8 g/kg were 595.10 ± 182.91 ng/mL, 5336.77 ± 1503.84 ng/mL·h and 850.46 ± 120 ng/mL, 9583.10 ± 888.92 ng/mL·h, respectively. The validated method was successfully applied to a pharmacokinetic study in rats after oral administration of KIOM-MA128.

scholarly journals Pharmacokinetic Comparison of Isoalantolactone and Alantolactone in Rats after Administration Separately by Optimization of an UPLC-MS2Method

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Renjie Xu ◽  
Mengyue Wang ◽  
Ying Peng ◽  
Xiaobo Li
Keyword(s):  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Rat Plasma ◽  
Sprague Dawley ◽  
Ionization Source ◽  
Fragment Ions ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass ◽  
Positive Ion

Isoalantolactone and alantolactone are two major active ingredients that are present in many medicinal plants. In this study, a sensitive and rapid ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed for determination of the two compounds in rat plasma, separately. In this method, an electrospray ionization source was applied and operated in positive ion mode; multiple reaction monitoring (MRM) was selected for quantification using target fragment ions 233.2→187.1 for isoalantolactone (alantolactone) and 245.1→189.1 for internal standard (IS). Retention time of the lactones and IS was within 3.0 min. Further calibration suggested a linear regression can be calculated within 2.5–500 ng/mL for isoalantolactone and 4–500 ng/mL for alantolactone. This method was used to compare the pharmacokinetic characteristics of isoalantolactone and alantolactone at a single dose of 5 mg/kg into male Sprague-Dawley rats by intravenous administration separately. The levels oft1/2, Kel, CL,Cmax, and AUC were significantly increased in the alantolactone group compared to isoalantolactone. These results suggested that isoalantolactone was distributed and eliminated more rapidly than alantolactone in rats when administered, respectively.

QUANTITATION OF CARVEDILOL OXIDATIVE METABOLITES IN HUMAN PLASMA USING LIQUID CHROMATOGRAPHY TANDEM MASS SPECTROMETRY

INDIAN DRUGS ◽  
2012 ◽  
Vol 49 (02) ◽  
pp. 37-44
Author(s):  
J Valarmathy ◽  
◽  
T. Sudha ◽  
K. L. Kumar ◽  
S. L Joshua
Keyword(s):  
Human Plasma ◽  
Room Temperature ◽  
Plasma Sample ◽  
Liquid Extraction ◽  
Liquid Liquid Extraction ◽  
Chromatography Tandem Mass Spectrometry ◽  
Oxidative Metabolites ◽  
Liquid Chromatography Tandem Mass ◽  
Assay Precision

A sensitive and efficient method was developed for the determination of carvedilol and its metabolite in human plasma by LC-MS/MS. Plasma samples were hydrolysed with beta-glucuronidase and the target compounds were extracted with liquid liquid extraction using diethyl ether in dichloro methane as solvent. The extracts were completely derivatized and analysed by LC-MS/MS. The linearity of the assay ranges from 0.250 ng/mL to 200.0 ng/mL for carvedilol and from 0.500 ng/mL to 30.0 ng/mL for 4-hydroxy carvedilol. The absolute recovery of carvedilol and its metabolite added to blank plasma sample was 70.28 82.90%. The reproducibility was from 0.96 to 8.28 for the intraday assay and from 1.65 to 6.09 for the interday assay precision. Repetitive thawing and freezing did not have an affect on metabolite through a minimum of three cycles. Thawed samples remaining in plasma for 4h before extraction were with 5% of theoretical value. Stability of the extracted samples on the auto sampler at room temperature was evaluated for 34 h and was observed to with in 12% of a fresh analytical sample for 4 hydroxy carvedilol. The proposed LC-MS/MS method was effective for the determination of carvedilol and it metabolite in human plasma.

scholarly journals A Rapid UPLC-MS Method for Quantification of Gomisin D in Rat Plasma and Its Application to a Pharmacokinetic and Bioavailability Study

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1403 ◽  
Author(s):  
Xiaoyong Zheng ◽  
Feng Feng ◽  
Xiunan Jiang ◽  
Jieying Qiu ◽  
Xiaojun Cai ◽  
...  
Keyword(s):  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Ionization Source ◽  
Quality Marker ◽  
Liquid Chromatography Tandem Mass ◽  
Bioavailability Study ◽  
Multiple Reaction Monitoring Mode ◽  
Positive Ion

Gomisin D, a lignan compound isolated from Fructus Schisandra, is a potential antidiabetic and anti-Alzheimer’s agent. Recently, gomisin D was used as a quality marker of some traditional Chinese medicine (TCM) formulas. In this study, a rapid ultra-performance liquid chromatography/tandem mass spectrometry method (UPLC-MS/MS) was developed and validated to quantify gomisin D in rat plasma for a pharmacokinetic and bioavailability study. Acetonitrile was used to precipitate plasma proteins. Separations were performed on a BEH C18 column with a gradient mobile phase comprising of acetonitrile and water (0.1% formic acid). An electrospray ionization source was applied and operated in the positive ion mode. The multiple reaction monitoring mode (MRM) was utilized to quantify gomisin D and nomilin (internal standard, IS) using the transitions of m/z 531.2 → 383.1 and m/z 515.3 → 161.0, respectively. The calibration curve was linear over the working range from 1 to 4000 ng/mL (R2 = 0.993). The intra- and interday precision ranged from 1.9% to 12.9%. The extraction recovery of gomisin D was in the range of 79.2–86.3%. The validated UPLC-MS/MS method was then used to obtain the pharmacokinetic characteristics of gomisin D after intravenous (5 mg/kg) and intragastric (50 mg/kg) administration to rats. The bioavailability of gomisin D was 107.6%, indicating that this compound may become a promising intragastrical medication. Our results provided useful information for further preclinical studies on gomisin D.

scholarly journals Pharmacokinetic and Bioavailability Studies of Galgravin after Oral and Intravenous Administration to Rats Using HPLC-MS/MS Method

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Lulu Zhao ◽  
Songrui Wang ◽  
Xuhua Huang ◽  
Yuqi Fan ◽  
Zixiang Xue ◽  
...  
Keyword(s):  
High Performance ◽  
Internal Standard ◽  
Rat Plasma ◽  
Reversed Phase ◽  
Future Research ◽  
Limit Of Quantitation ◽  
Liquid Chromatography Tandem Mass ◽  
Positive Ion ◽  
Interday Precision

This paper presents a new high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method with a rapid analysis of 6 min to determine the concentration of galgravin in rat plasma so as to study its pharmacokinetic features and bioavailability in vivo. Schisandrin was selected as the internal standard (IS). After extracting the analyte from plasma samples with ethyl acetate, methanol-H2O (0.1% formic acid) (85 : 15, v / v ) was used as mobile phase to achieve chromatographic separation on a C18 reversed phase column. The MS detection was performed in positive ion mode using electrospray ionization (ESI) source. This method showed good linearity over the range of 1~500 ng/mL ( R 2 > 0.999 ), and the lower limit of quantitation (LLOQ) was 1.0 ng/mL. The intraday precision and interday precision were both within 8.5%, whereas the accuracies were in the range of -2.6%–6.0%. The average recoveries of galgravin in rat plasma were between 92.3% and 99.3%. Moreover, galgravin was stable throughout storage and processing with all RSDs below 12.1%. After the successful application of this optimized method, the oral bioavailability of galgravin was determined to be 8.5%. This study will be helpful to the future research and development of galgravin.

scholarly journals MEASUREMENT OF CORTISOL AND CORTISONE IN HUMAN SALIVA BY UPLC-MS/MS

2021 ◽  
pp. 54-58
Author(s):  
SYED N. ALVI ◽  
MUHAMMAD M. HAMMAMI
Keyword(s):  
Simultaneous Measurement ◽  
Room Temperature ◽  
Ammonium Acetate ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Human Saliva ◽  
Coefficients Of Variation ◽  
Liquid Chromatography Tandem Mass ◽  
Transition Set ◽  
Positive Ion

Objective: To develop and validate a simple and rapid assay for simultaneous measurement of cortisol and cortisone in human saliva by ultra-performance liquid chromatography-tandem mass spectrometry. Methods: Chromatographic analysis was performed on an Atlantis dC18 column (2.1 x 100 mm, 3 µm) using a mobile phase consisting of acetonitrile and 2 mmol ammonium-acetate (50:50, v; v) that was delivered at a flow rate of 0.3 ml/min. The eluents were monitored using electrospray ionization in the positive ion mode set at transition set of mass-to-charge (m/z): 363.11 → 121.00, 361.18 → 163.11, and 367.19 → 121.24 for cortisol, cortisone and internal standard (IS), respectively the method was validated for linearity, accuracy, precision, and recovery, according to international guidelines. Results: The retention times of cortisol, cortisone and internal were about 1.38, 1.43 and 1.38 min, respectively. Cortisol level and cortisone level relationship to the ratio of their respective peak-area to IS’s peak-area was linear (range of 0.5-100 ng/ml). Coefficients of variation and inaccuracy were, ≤9.9% and-0.3 to 6.9 for cortisol and ≤8.4 and-1.5 to 4.8 for cortisone, respectively. Extraction recoveries for cortisol, cortisone, and the IS were 90%, 94%, and 98%, respectively. Cortisol and cortisone stability was evaluated in processed saliva samples (stored at room temperature for 24 h) and unprocessed saliva samples (stored at room temperature for 24 h or at-20 °C for 10 w) and after 3 freeze-thaw cycles was ≥ 86%. Conclusion: The proposed method is simple, precise, and accurate for the rapid simultaneous measurement of cortisol and cortisone levels in saliva. The assay was successfully applied to determine levels of cortisol and cortisone in human saliva samples obtained from healthy volunteers.

scholarly journals Rapid Determination of Fumonisins in Corn-Based Products by Liquid Chromatography/Tandem Mass Spectrometry

2010 ◽  
Vol 93 (5) ◽  
pp. 1472-1481 ◽  
Author(s):  
Wei Li ◽  
Timothy J Herrman ◽  
Susie Y Dai
Keyword(s):  
Liquid Chromatography ◽  
Animal Feed ◽  
Rapid Determination ◽  
Fumonisin B1 ◽  
Ultra Performance Liquid Chromatography ◽  
Sample Volume ◽  
High Throughput Analysis ◽  
Accuracy And Precision ◽  
Liquid Chromatography Tandem Mass

Abstract A simple, fast, and robust method was developed for the determination of fumonisin B1 (FB1), fumonisin B2 (FB2), and fumonisin B3 (FB3) in corn-based human food and animal feed (cornmeal). The method involves a single extraction step followed by centrifugation and filtration before analysis by ultra-performance liquid chromatography/electrospray ionization (UPLC/ESI)-MS/MS. The LC/MS/MS method developed here represents the fastest and simplest procedure (<30 min) among both conventional HPLC methods and other LC/MS methods using SPE cleanup. The potential for high throughput analysis makes the method particularly beneficial for regulatory agencies and analytical laboratories with a high sample volume. A single-laboratory validation was conducted by testing three different spiking levels (200, 500, and 1000 ng/g for FB1 and FB2; 100, 250, and 500 ng/g for FB3) for accuracy and precision. Recoveries of FB1 ranged from 93 to 98% with RSD values of 3-8%. Recoveries of FB2 ranged from 104 to 108, with RSD values of 2-6%. Recoveries of FB3 ranged from 94% to 108%, with RSD values of 2-5%.

Simultaneous Determination of Rosuvastatin, Rosuvastatin-5 S-lactone, and N-desmethyl Rosuvastatin in Human Plasma by UPLC-MS/MS and Its Application to Clinical Study

Drug Research ◽  
2017 ◽  
Vol 68 (06) ◽  
pp. 328-334 ◽  
Author(s):  
Xue Bai ◽  
Xi-Pei Wang ◽  
Guo-Dong He ◽  
Bin Zhang ◽  
Min Huang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Clinical Study ◽  
Human Plasma ◽  
Ultra Performance Liquid Chromatography ◽  
Internal Standards ◽  
Liquid Chromatography Tandem Mass ◽  
Artery Disease ◽  
Acquity Uplc ◽  
Positive Ion

Abstract Objective A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay was developed and validated for the simultaneous quantification of rosuvastatin (RST), rosuvastatin-5 S-lactone (RSTL), and N-desmethyl rosuvastatin (DM-RST) in human plasma. Methods Sample was prepared by liquid-liquid extraction with ethyl acetate from 100 μL acidulated buffered plasma. Then analytes were chromatographically separated using an Acquity UPLC HSS T3 column (3.0 mm×100 mm, 1.8 µm) by 0.1% formic acid and gradient acetonitrile at a flow rate of 0.30 mL/min. Three analytes and internal standards (carbamazepine) were eluted in 3.5 min. Mass spectrometry detection was performed through positive ion electrospray ionization (ESI). Results The calibration curves for three analytes were linear (R≥0.9987, n=3) within the concentration range of 0.1–50 ng/mL for RST and RSTL, and 0.2–100 ng/mL for DM-RST. Mean extraction recoveries were enhanced by means of acidulated plasma using ammonium acetate of pH 4.0, which ranged within 75.3–98.8% for three analytes. Intra- and inter precision and accuracy were 88.2–96.4%. Conclusions This present method was lower LLOQ, less time consuming (3.5 min), less plasma consuming (100 µL) and simpler sample preparation. And it was successfully applied to determine steady state concentrations of RST, RSTL and DM-RST in a clinical study of RST for patients with coronary artery disease (CAD).

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