Figure 1 - uploaded by Reshan Fernando
Content may be subject to copyright.
Source publication
A rapid and simple liquid chromatography tandem mass spectrometry method was developed and validated for the simultaneous determination of L-ephedrine, pseudoephedrine, and caffeine in male Fisher-344 rat plasma at nanogram-per-milliliter concentrations for use in support of toxicology studies. Only 25 μL of plasma is required, and extraction is pe...
Context in source publication
Similar publications
A liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for the determination of therapeutic levels of caffeine in dried blood spot (DBS) samples. Caffeine is used in the treatment of Apnoea of Prematurity (AoP) in newborn children. Calibration DBS samples were prepared by spotting 15 μL of whole blood spiked with the a...
A rapid and sensitive high-performance liquid chromatographic method has been developed and validated for the simultaneous determination and quantification of cephalosporins (cefpirome, cefaclor, ceftazidime, and cephradine) in pharmaceutical formulations. Separation was achieved in the presence of caffeine as internal standard on a Mediterranea C1...
A simple, precise, and rapid high performance liquid chromatography (HPLC) method for the determination of acetaminophen level in human plasma using caffeine as an internal standard (IS) was developed and validated. 0.5 ml plasma samples containing acetaminophen were mixed with 50 µg of the IS. After adding 30 µl of 50% perchloric acid, the mixture...
A reversed-phase high performance liquid chromatographic method was improved for the simultaneous determination of theobromine, paraxanthine, theophylline, and caffeine in urine. The method includes a liquid-liquid extraction at alkaline pH with ethylacetate. The 7-(2,3-dihidroxypropyl) theophylline was used as an internal standard (ISTD). The sepa...
A simple, precise, and rapid high performance liquid chromatography (HPLC) method for the determination of acetaminophen level in human plasma using caffeine as an internal standard (IS) was developed and validated. 0.5 ml plasma samples containing acetaminophen were mixed with 50 µg of the IS. After adding 30 µl of 50% perchloric acid, the mixture...
Citations
... For ephedrine and allied substances, traditionally used pretreatments and traditional LLE meet most analysis requirements of various matrix, but their low extraction efficiency and time-consuming nature for complex samples remain as major drawbacks. SPE is a highly selective and efficient extraction method with high requirements, which has been used for the pretreatment of biological samples (e.g., hair, humor, pericardial fluid, blood, urine, etc.) [15,30,31,34,35,40,52] and water in the environment [70,[72][73][74][75]. Various microextraction technologies based on LLE or SPE (such as LLME and SPME) using new materials and design applications, provide a more ecofriendly, inexpensive and efficient option for ephedrine extraction. Microextraction technologies have demonstrated excellent performance in the pretreatment of biological samples [16][17][18]23,28,29,43,46,[48][49][50]53] and methamphetamine samples [63,65], which can achieve trace analysis. ...
... The application of novel materials (e.g., MIP material made with MAA/EDMA/CHCl 3 ) and techniques (e.g., MHPLC, 2D-LC) have significantly improved the separation potential of chromatography and the resolution of MS, providing more options for the analysis of complex samples or high throughput screening of unknown samples. LC based technology is widely used, showing good analytical performance in the analysis of targets in plants [86,87,99], wastewater [74,75], biological liquids [21,24,35] and various pharmaceutical preparations [5,106,108]. GC based technology is rarely used in the analysis of ephedrine due to the need for derivation process, among which the analysis of targets in biological samples [20,23,30,31,46,47] is the most common. ...
... However, these methods have some limitations, given the complicated sample processing procedure and low sensitivity. In addition, previous studies have described liquid chromatography with tandem mass spectrometry detection (LC-MS/MS), which was reportedly simpler and more sensitive for analyzing six ephedra alkaloids in dietary supplements and biological fluids [16], as well as ephedrine and pseudoephedrine in rat plasma and horse urine [17][18][19]. LC-MS/MS was employed for determining nine herbal phenalkylamines in human plasma, including ephedrine and pseudoephedrine [20]. However, this method was developed with a 10 ng/mL detection limit and was not applied for pharmacokinetic investigations. ...
A sensitive and reproducible liquid chromatography-tandem mass spectrometry (LC-MS/MS) system was developed and fully validated for the simultaneous determination of ephedrine and pseudoephedrine in human plasma after oral administration of the herbal prescription Ojeok-san (OJS); 2-phenylethylamine was used as the internal standard (IS). Both compounds presented a linear calibration curve (r2 ≥ 0.99) over a concentration range of 0.2–50 ng/mL. The developed method was fully validated in terms of selectivity, lower limit of quantitation, precision, accuracy, recovery, matrix effect, and stability, according to the regulatory guidelines from the U.S. Food and Drug Administration and the Korea Ministry of Food and Drug Safety. This validated method was successfully applied for the pharmacokinetic assessment of ephedrine and pseudoephedrine in 20 healthy Korean volunteers administered OJS.
... Phytochemical and pharmacological studies revealed that EH, PEH exerted significant diaphoretic, antitussive, and antiasthmatic effects, and MEH exerted primary antitussive and antiasthmatic effects. Moreover, these three ephedrines were the main biologically active ingredients in ephedra [8,[27][28][29][30][31][32][33][34]. ...
Ephedra have been used as a common traditional Chinese medicine for thousands of years. However, the perspiration effect of the unprocessed ephedra was too strong. Clinical trials have shown that processing methods play a critical role in moderating the perspiration property of ephedra according to the needs. A LC-MS/MS method was developed and validated to compare the pharmacokinetic properties of the three ephedrines after oral administration of unprocessed and honey-fried ephedra extract. The contents of honey, frying temperature, and frying time were set at 20%, 116°C, and 7 min by the Box-Behnken response surface method, respectively. In the pharmacokinetics study, the biosamples were pretreated and extracted by protein precipitation method with acetonitrile and separated on an Agilent TC-C 18 column (250 mm × 4.6 mm, 5 μ m) using a mobile phase consisting of 0.1% formic acid methanol and 5 mM ammonium acetate aqueous solution (5 : 95, v/v). All calibration curves were linear ( r>0.9932 ) with lower limits of quantitation (LLOQs) < 12 ng/mL. The mean recoveries of the three analytes were higher than 75%. The pharmacokinetics study indicated that the reduced absorption of ephedrine hydrochloride (EH) and pseudoephedrine hydrochloride (PEH) in honey-fried ephedra group might be the main reason for the moderation of the diaphoretic property.
... In order to elucidate the mechanisms of action of MX components in vivo, quantitative methods for determining their levels in plasma samples and pharmacokinetic profiles are needed. There have been several reports concerning the quantification of ephedra alkaloids [9][10][11] and amygdalin [12,13] in plasma. However, simultaneous pharmacokinetic studies of ephedra alkaloids, amygdalin, and prunasin have not been reported after oral administration of Mahuang-Xingren aqueous extract in rats. ...
The purpose of this study was to develop a method for simultaneous analysis of schizandrin, ephedrine, paeoniflorin, and cinnamic acid as constituents of Socheongryong-tang tablet in human plasma using UPLC-MS/MS. These four components were separated using water containing 0.01% formic acid and methanol as a mobile phase by gradient elution at a flow rate of 0.3 mL/min with a HALO-C18 column (2.1 mm × 100 mm, 2.7 μm particle size). Quantitation was performed on a triple quadrupole mass spectrometer employing electrospray ionization technique operated in multiple reaction monitoring mode. Mass transitions were m/z 432.9 → 384.1 for schizandrin, 165.8 → 148.1 for ephedrine, 525.0 → 449.2 for paeoniflorin, 146.8 → 102.9 for cinnamic acid, and 340.0 → 324.0 for papaverine as internal standard. Liquid-liquid extraction and protein precipitation with ethyl acetate-methanol (1:2, v/v) were used to obtain these four components. Chromatograms showed high resolution, sensitivity, and selectivity without interference by plasma constituents. Calibration curves of schizandrin, ephedrine, paeoniflorin, and cinnamic acid in human plasma ranged from 0.02 to 8 ng/mL, 0.5 to 200 ng/mL, 0.2 to 80 ng/mL, and 1 to 400 ng/mL, respectively. Calibration curves of each analyte displayed excellent linearity, with correlation coefficients > 0.99. For all four components, both intra- and inter-day precisions (CV%) were <5.99%. The accuracy was 99.35-103.30% for schizandrin, 98.48-104.38% for ephedrine, 97.06-103.34% for paeoniflorin, and 99.97-104.36% for cinnamic acid. This analytical method developed in this study satisfied the criteria of international guidance. It could be successfully applied to pharmacokinetic studies of schizandrin, ephedrine, paeoniflorin, and cinnamic acid after oral administration of Socheongryong-tang tablet to humans.
Background and objectives:
Ephedra alkaloids, including ephedrine (EP), pseudoephedrine (PEP) and methylephedrine (MEP), are sympathomimetic compounds with known toxicities but many Ephedra (Ephedrae herba) preparations, such as Ephedra decoction, have been clinically applied for centuries. In order to explore the possible detoxification mechanism of Ephedra alkaloids, four representative compounds in Ephedra decoction (cinnamic acid, amygdalin, glycyrrhizic acid and liquiritin) were studied for their pharmacokinetic effects on Ephedra alkaloids in Sprague-Dawley rats.
Methods:
Animals were randomly divided into six groups, with six rats in each. Rats were treated orally with EP-PEP-MEP (20 mg/kg EP + 20 mg/kg PEP + 20 mg/kg MEP) and different combinations of cinnamic acid (3.03 mg/kg), amygdalin (56.97 mg/kg), glycyrrhizic acid (12.42 mg/kg), liquiritin (3.79 mg/kg) with EP-PEP-MEP, and 20 mg/kg EP + 20 mg/kg PEP + 20 mg/kg MEP + 3.03 mg/kg cinnamic acid + 56.97 mg/kg amygdalin + 12.42 mg/kg glycyrrhizic acid + 3.79 mg/kg liquiritin. Blood samples (0.5 mL) were taken from the orbital sinus venous plexus into heparinized tubes at 5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300 and 360 min (6 rats per time point in each group) following single administration. The concentrations of Ephedra alkaloids in rat plasma were determined using a validated high performance liquid chromatography method.
Results:
Area under the concentration-time curve from 0 to 360 min (AUC0-t) of EP, PEP and MEP were 666.99, 650.76 and 632.37 µg·min/mL, respectively. Maximum plasma concentration (Cmax) of EP, PEP and MEP were 4.15, 4.08 and 3.59 μg/mL, respectively. Mean residence time (MRT) of EP, PEP and MEP were 197.00, 173.97 and 183.87 min, respectively, when the rats were treated with EP-PEP-MEP. Cinnamic acid increased the AUC0-tof EP while decreased Cmaxof EP, amygdalin and glycyrrhizic acid increased Cmaxand AUC0-tof EP and PEP, while liquiritin decreased AUC0-tof EP and PEP. The four representative compounds reduced MRT of EP, PEP and MEP, four compounds decreased AUC0-tof MEP. The EP-PEP-MEP + cinnamic acid + amygdalin + glycyrrhizic acid + liquiritin group increased AUC0-tof EP while decreased MRT of EP, increased MRT of PEP while decreased AUC0-tof PEP. The EP-PEP-MEP + cinnamic acid + amygdalin + glycyrrhizic acid + liquiritin group decreased MRT, AUC0-tand Cmaxof MEP.
Conclusions:
Significant changes in pharmacokinetic parameters of EP, PEP and MEP were observed after oral administration with different combinations. The pharmacokinetic results reported here might provide reference for clinical usage of Ephedra alkaloids.
The main representatives of narcotic substances of natural origin are considered. Methodological solutions used in their screening, identification, and quantitative determination in raw materials, dosage forms, and biological materials are discussed. Prospects of application of state-of-the art hybrid methods combining chromatographic separation with mass spectrometric determination are noted.
The combination of Herba Ephedrae (Mahuang in Chinese) and Radix Aconiti Lateralis (Fuzi in Chinese) is a classical preparation in traditional Chinese medicine and used for treating colds and rheumatic arthralgia. However, herbal medicines containing ephedrines and Aconitum alkaloids are strictly regulated because of the potential for adverse effects on the cardiovascular system and the central nervous system. We aimed to investigate the pharmacokinetics of 11 alkaloids in the Mahuang-Fuzi combination and single-herb extracts after oral administration in rats. The alkaloids were norephedrine, norpseudoephedrine, ephedrine, pseudoephedrine, methylephedrine, aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine. Simultaneous determination of the alkaloids, including two pairs of diastereomers, was achieved in 14.5 min by a simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method. The separation was performed on a Zorbax SB-Aq column (100 mm × 2.1 mm, 3.5 μm) at a flow rate of 0.3 mL/min using acetonitrile-0.1% formic acid aqueous solution as the mobile phase. The validated method demonstrated adequate sensitivity, selectivity and process efficiency for the quantitative analysis of complex herbal components. Compared with single-herb extracts, alkaloids in plasma (except methylephedrine, benzoylmesaconine and benzoylhypaconine) showed slower elimination (the mean residence time or half-life was longer), although the maximum plasma concentration and area under the plasma concentration curve values decreased. Accumulation may occur with continuous drug intake. These results suggest that drug monitoring may be essential for the safe use of the Mahuang-Fuzi combination.
A rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry method was developed and validated for the determination and quantification of ephedrine in rat plasma samples. An Acquity UPLC BEH C18 column (1.7 μm, 2.1 mm × 50 mm) was used for chromatographic separation. Electrospray ionization in the positive mode was used, and the precursor-fragment ion pairs of m/z 166/148 and m/z 289/97 were adopted to characterize ephedrine and testosterone (internal standard), respectively. The method was validated using 10, 100 and 500 ng/mL of ephedrine. It demonstrated adequate levels of precision and accuracy, matrix effect, extraction recovery and stability. Linearity over the concentration range of 0.5-2000 ng/mL was acceptable with a correlation coefficient (r²) better than 0.990. To determine the pharmacokinetic behaviour of this sympathomimetic compound in the Sprague-Dawley rats, ephedrine hydrochloride, Herba Ephedrae single-herb and Wu Tou Tang decoctions were administered orally, and ephedrine hydrochloride was also administered by intravenous injection, and blood samples were collected over 24 h. Ephedrine was measured in plasma and pharmacokinetic parameters were determined by using the standard non-compartmental method and calculated by using Practical Pharmacokinetic Program-Version 87/97. The AUC(0-t) and T(max) values were significantly different (p < 0.05). Ephedrine AUC(0-t) values were significantly lower following the Wu Tou Tang decoction compared to the other oral treatments, suggesting that some components in the decoction may reduce the bioavailability of ephedrine.
