Pharmacokinetic study of hypaphorine, a potential agent for treating osteoclast-based bone loss, on rats using LC-MS/MS

2021 ◽  
Vol 25 ◽  
Author(s):  
Taiyuan Zhang ◽  
Yan Yan ◽  
Yutao Xue ◽  
Shan Xiong ◽  
Wenwen Ran ◽  
...  
Keyword(s):  
Bone Loss ◽  
High Performance ◽  
Rat Plasma ◽  
Selected Reaction Monitoring ◽  
Extraction Recovery ◽  
Accuracy And Precision ◽  
Liquid Chromatography Tandem Mass ◽  
Matrix Factors ◽  
Gradient Mode

Aim and Objective: A high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of hypaphorine, a potential agent for treating osteoclast-based bone loss, was developed and valadated in rat plasma. Materials and Methods: Plasma samples were pretreated by the protein precipitation. Chromatographic separation was performed using an Inertsil ODS-3 column (50 mm × 4.6 mm, 5 μm). The mobile phase consisted of water (containing 0.1% formic acid) and acetonitrile in a gradient mode at a flow rate of 0.5 mL/min. The acquisition was carried out in selected reaction monitoring (SRM) of the transitions from protonated precursor ion [M + H]+ to the particular daughter ion and the mass transitions of hypaphorine and IS were 247 → 188 and m/z 219 → 188, respectively. The method was validated in terms of selectivity, linearity, accuracy and precision, extraction recovery and matrix effect, stability and carryover. Results: It showed good linearity over the range of 1-2000 ng/mL (R2 = 0.9978). The intra-batch accuracy was within 93.95-105.81% and the precision was within 4.92-11.53%. The inter-batch accuracy was within 96.18-100.39% with a precision of 6.22-11.23%. The extraction recovery and matrix factors were acceptable. Conclusion: The simple and rapid method was successfully applied to the pharmacokinetics study in rats following oral administration of hypaphorine at the doses of 0.5, 1.5, and 4.5 mg/kg.

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 Simplified and Rapid Determination of Primaquine and 5,6-Orthoquinone Primaquine by UHPLC-MS/MS: Its Application to a Pharmacokinetic Study

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4357
Author(s):  
Waritda Pookmanee ◽  
Siriwan Thongthip ◽  
Jeeranut Tankanitlert ◽  
Mathirut Mungthin ◽  
Chonlaphat Sukasem ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
High Performance ◽  
Rapid Determination ◽  
Active Metabolites ◽  
Chromatography Tandem Mass Spectrometry ◽  
Accuracy And Precision ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass ◽  
Isocratic Mode

The method for the determination of primaquine (PQ) and 5,6-orthoquinone primaquine (5,6-PQ), the representative marker for PQ active metabolites, via CYP2D6 in human plasma and urine has been validated. All samples were extracted using acetonitrile for protein precipitation and analyzed using the ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) system. Chromatography separation was carried out using a Hypersil GOLDTM aQ C18 column (100 × 2.1 mm, particle size 1.9 μm) with a C18 guard column (4 × 3 mm) flowed with an isocratic mode of methanol, water, and acetonitrile in an optimal ratio at 0.4 mL/min. The retention times of 5,6-PQ and PQ in plasma and urine were 0.8 and 1.6 min, respectively. The method was validated according to the guideline. The linearity of the analytes was in the range of 25–1500 ng/mL. The matrix effect of PQ and 5,6-PQ ranged from 100% to 116% and from 87% to 104% for plasma, and from 87% to 89% and from 86% to 87% for urine, respectively. The recovery of PQ and 5,6-PQ ranged from 78% to 95% and form 80% to 98% for plasma, and from 102% to from 112% to 97% to 109% for urine, respectively. The accuracy and precision of PQ and 5,6-PQ in plasma and urine were within the acceptance criteria. The samples should be kept in the freezer (−80 °C) and analyzed within 7 days due to the metabolite stability. This validated UHPLC-MS/MS method was beneficial for a pharmacokinetic study in subjects receiving PQ.

scholarly journals Preclinical Pharmacokinetics of Scoparone, Geniposide and Rhein in an Herbal Medicine Using a Validated LC-MS/MS Method

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2716 ◽  
Author(s):  
Tun-Pin Hsueh ◽  
Tung-Hu Tsai
Keyword(s):  
Bioactive Compounds ◽  
Pharmacokinetic Study ◽  
High Performance ◽  
Low Dose ◽  
Rat Plasma ◽  
Herbal Formula ◽  
Preclinical Pharmacokinetics ◽  
Pharmacokinetic Properties ◽  
Liquid Chromatography Tandem Mass

The herbal formula Yin-Chen-Hao-Tang has been reported to have anti-fibrosis properties. The aim of this study was to reveal the pharmacokinetic characteristics of bioactive compounds in this herbal formula. A new high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of scoparone, geniposide and rhein in rat plasma. A pharmaceutical herbal powder was administered to rats at doses of 1 g/kg and 3 g/kg orally. The method showed excellent linearity (r2 > 0.999) and validation was successfully conducted for the pharmacokinetic study. The results show that the Cmax values and areas under the curve of scoparone, geniposide and rhein were higher and not proportional to the dose in rat plasma, while the Tmax and half-life values were consistent in the group that received 1 g/kg. The clearance of the higher dose (3 g/kg) did not decrease proportionally to that of the low dose. The results showed the nonlinear pharmacokinetic properties of scoparone, geniposide and rhein in Yin-Chen-Hao-Tang that suggested possible accumulation of bioactive compounds through oral administration. This pharmacokinetic study reveals that an increased dose of this herbal formula would largely increase the maximum concentration and bioavailability of scoparone, geniposide and rhein.

scholarly journals Pharmacokinetics and pharmacodynamics of cyclopropylfentanyl in male rats

2021 ◽  
Author(s):  
Marianne Skov-Skov Bergh ◽  
Inger Lise Bogen ◽  
Nancy Garibay ◽  
Michael H. Baumann
Keyword(s):  
High Performance ◽  
Parent Drug ◽  
Rat Plasma ◽  
Male Rats ◽  
Sprague Dawley ◽  
Limit Of Quantification ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass ◽  
Blood Specimens

Abstract Background Illicitly manufactured fentanyl and its analogs are a major driving force behind the ongoing opioid crisis. Cyclopropylfentanyl is a fentanyl analog associated with many overdose deaths, but limited knowledge is available about its pharmacology. In the present study, we developed a bioanalytical method for the determination of cyclopropylfentanyl and its main metabolite cyclopropylnorfentanyl and evaluated pharmacokinetic-pharmacodynamic relationships in rats. Method An ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for determination of cyclopropylfentanyl and cyclopropylnorfentanyl in rat plasma. Male Sprague–Dawley rats fitted with jugular catheters and temperature transponders received cyclopropylfentanyl (30, 100, and 300 μg/kg) or saline subcutaneously. Blood specimens were withdrawn over an 8-h time period, along with measurements of pharmacodynamic endpoints. Results The analytical method was validated, and both analytes exhibited a low limit of quantification (15 pg/mL). Cyclopropylfentanyl caused dose-related increases in hot plate latency (ED50 = 48 µg/kg) and catalepsy (ED50 = 87 µg/kg) and produced long-lasting hypothermia at the highest dose. Plasma cyclopropylfentanyl rose rapidly in a dose-related fashion, reaching maximal concentration (Cmax) after 15–28 min, whereas metabolite Cmax occurred later at 45–90 min. Cyclopropylfentanyl Cmax values were similar to concentrations measured in non-fatal intoxications in humans; however, differences in parent drug: metabolite ratio indicated possible interspecies variance in metabolism. Conclusion Our study shows that cyclopropylfentanyl produces typical opioid-like effects in male rats. Cyclopropylfentanyl displays much greater analgesic potency when compared to morphine, suggesting that cyclopropylfentanyl poses increased overdose risk for unsuspecting users.

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