Chemical profiling and characterization of phenolic acids,flavonoids, terpene glycosides from Vangueria agrestis using ultra-high-performance liquid chromatography/ion mobility quadrupole time-of-flight mass spectrometry and metabolomics approach

Vangueria agrestis is a shrub indigenous to tropical Africa, belonging to family Rubiaceae and is traditionally used as a decoction for treatment of fever, pain, and malaria. This study was undertaken to investigate the chemical constituents based on precursor exact mass and fragment ion information. The chemical profiling and structural characteristics of chemical constituents from methanolic extracts of dried aerial parts and roots of V. agrestis and dietary supplements were analyzed using ultra-high-performance liquid chromatography/ion mobility quadrupole time-of-flight mass spectrometry coupled with UNIFI platform and multivariate analysis in both negative and positive ion modes. A non-targeted ultra-high-performance liquid chromatography-mass spectrometry analysis was carried out to profile the chemical constituents of crude extracts of V. agrestis, and 73 compounds, including reference compounds, were identified. The fragments of flavonoids, monoterpene, and triterpene glycosides revealed the characteristic cleavage of glycosidic linkages, and the fragmentation pattern provided the identity of the sugars. This analytical method provides a quick method for quality assessment of dietary supplements. Finally, a chemometrics approach with multivariate statistical tools was used to visualize the differences between root and aerial parts of plant samples and to find the potential chemical markers that differentiate among these parts of V. agrestis samples and dietary supplements.     

Simultaneous Determination of Isoquinoline Alkaloids in Medicinal Asiatic Plants by Ultrasound-Assisted Extraction and High-Performance Liquid Chromatography – Mass Spectrometry with Principal Component Analysis

Isoquinoline alkaloids (papaverine, noscapine, berberine, emetine, and quinine) were determined in medicinal plants and herbs used in Traditional Chinese Medicine and Ayurveda by liquid chromatography with tandem mass spectrometry detection (LC-MS/MS). The analyzed alkaloids were separated at gradient conditions using methanol and 2% acetic acid within 12?min. The validated method was successfully applied for 17 herbal samples: Ashwagandha, Astragalus membranaceus, Emblica officinalis, Mucuna pruriens, Pueraria lobata, Ocimum sanctum, Rehmannia glutinosa, Schisandra sinensis, Terminalia arjuna, Terminalia chebula, and dietary supplements. The highest concentration of studied alkaloids was observed for berberine in Puearia lobata (6.68?±?0.62?mg 100?g^?1 d.m.), while the lowest value was obtained for noscapine in a dietary supplement containing Terminalia arjuna (0.09?±?0.01?mg 100?g^?1 d.m.). Principal component analysis, cluster analysis, and one-way ANOVA tests were also performed. The results indicate the need to control plant materials and dietary supplements in terms of the content of alkaloids and toxic components.     

Receptor-based high-throughput screening and identification of estrogens in dietary supplements using bioaffinity liquid-chromatography ion mobility mass spectrometry

A high-throughput bioaffinity liquid chromatography-mass spectrometry (BioMS) approach was developed and applied for the screening and identification of recombinant human estrogen receptor α (ERα) ligands in dietary supplements. For screening, a semi-automated mass spectrometric ligand binding assay was developed applying ¹³C_2, ¹⁵?N-tamoxifen as non-radioactive label and fast ultra-high-performance–liquid chromatography–electrospray ionisation–triple-quadrupole-MS (UPLC-QqQ-MS), operated in the single reaction monitoring mode, as a readout system. Binding of the label to ERα-coated paramagnetic microbeads was inhibited by competing estrogens in the sample extract yielding decreased levels of the label in UPLC-QqQ-MS. The label showed high ionisation efficiency in positive electrospray ionisation (ESI) mode, so the developed BioMS approach is able to screen for estrogens in dietary supplements despite their poor ionisation efficiency in both positive and negative ESI modes. The assay was performed in a 96-well plate, and all these wells could be measured within 3 h. Estrogens in suspect extracts were identified by full-scan accurate mass and collision-cross section (CCS) values from a UPLC-ion mobility-Q-time-of-flight-MS (UPLC-IM-Q-ToF-MS) equipped with a novel atmospheric pressure ionisation source. Thanks to the novel ion source, this instrument provided picogram sensitivity for estrogens in the negative ion mode and an additional identification point (experimental CCS values) next to retention time, accurate mass and tandem mass spectrometry data. The developed combination of bioaffinity screening with UPLC-QqQ-MS and identification with UPLC-IM-Q-ToF-MS provides an extremely powerful analytical tool for early warning of ERα bioactive compounds in dietary supplements as demonstrated by analysis of selected dietary supplements in which different estrogens were identified.

Quality assessment of traditional Chinese medicine herb couple by high‐performance liquid chromatography and mass spectrometry combined with chemometrics

This study was designed to develop a simple, specific and reliable method to overall analyze the chemical constituents in clematidis radix et rhizome/notopterygii rhizome et radix herb couple using high‐performance liquid chromatography coupled with tandem mass spectrometry and multiple chemometric analysis. First, the separation and qualitative analysis of herb couple was achieved on an Agilent Zorbax Eclipse Plus C₁₈ column (250 mm × 4.6 mm, 5 μm), and 69 compounds were unambiguously or tentatively identified. Moreover, in quantitative analysis, eight ingredients including six coumarins and two triterpenoid sapogenins were quantified by high‐performance liquid chromatography coupled with tandem mass spectrometry. In terms of good linearity (r² ≥ 0.9995) with a relatively wide concentration range, recovery (85.40–102.50%) and repeatability (0.99–4.45%), the validation results suggested the proposed method was reliable, and successfully used to analyze ten batches of herb couple samples. Then, hierarchical cluster analysis and principal component analysis were used to classify samples and search significant ingredients. The results showed that ten batches of herb couple samples were classified into three groups, and six compounds were found for its better quality control.     

A flow-injection mass spectrometry fingerprinting method for authentication and quality assessment of Scutellaria lateriflora-based dietary supplements

Scutellaria lateriflora, commonly known as skullcap, is used as an ingredient in numerous herbal products. However, it has been occasionally adulterated/contaminated with Teucrium canadense and/or Teucrium chamaedrys, commonly known as germander, due to the morphological similarities between the two genera. The latter contains hepatotoxic diterpenes. Despite the potential hepatotoxicity introduced by germander contamination, analytical methodologies for the authentication and quality assessment of S. lateriflora-based dietary supplements have not been reported. In this study, a flow-injection/mass spectrometry fingerprinting method in combination with principal component analysis was used to survey S. lateriflora-based dietary supplements sold in the USA.     

Chemical fingerprint analysis and quantitative determination of steroidal compounds from Dioscorea villosa,Dioscorea species and dietary supplements using UHPLC‐ELSD

Ultra high‐performance liquid chromatography (UHPLC) with evaporative light scattering detection was used for the quantification of steroidal saponins and diosgenin from the rhizomes or tubers of various Dioscorea species and dietary supplements that were purported to contain Dioscorea. The analysis was performed on an Acquity UPLC? system with an UPLC? BEH Shield RP₁₈ column using a gradient elution with water and acetonitrile. Owing to their low UV absorption, the steroidal saponins were observed by evaporative light scattering detection. The 12 compounds could be separated within 15 min using the developed UHPLC method with detection limits of 5–12 µg/mL with 2 μL injection volume. The analytical method was validated for linearity, repeatability, accuracy, limits of detection and limits of quantification. The relative standard deviations for intra‐ and inter‐day experiments were <3.1%, and the recovery efficiency was 97–101%. The total content of standard compounds was found to be in the ranges 0.01–14.5% and 0.9–28.6 mg daily intake for dry plant materials and solid commercial preparations, respectively. UHPLC–mass spectrometry with a quadrupole mass analyzer and ESI source was used only for confirmation of the identity of the various saponins. The developed method is simple, rapid and especially suitable for quality control analysis of commercial products. Copyright © 2013 John Wiley & Sons, Ltd.     

Study on chemical constituents and fingerprints of Phellodendron amurense Rupr. based on ultra-performance liquid chromatography–quadrupole–time-of-flight–mass spectrometry

The chemical constituents from Phellodendron amurense Rupr. were characterized systematically by ultra-performance liquid chromatography—quadrupole–time-of-flight–mass spectrometry method for collecting mass spectrometry data, and the fingerprints method was established, providing reference for its quality control. The chromatographic column was ACQUITY UPLC BEH-C₁₈ (100 mm×2.1 mm, 1.7 μm). The mobile phase was acetonitrile-0.1% formic acid aqueous solution and the compounds from P. amurense Rupr. were identified by Qualitative Analysis 10.0 software, reference substance, retention time, mass spectrometry fragmentation pattern and database retrieval. Meanwhile, liquid chromatography–mass spectrometry fingerprint methods of P. amurense Rupr. and Phellodendron chinense Schneid. were established by using the similarity evaluation system of chromatographic fingerprint of traditional Chinese medicine (2012 edition), and the differences were analyzed by multivariate statistical analysis methods. A total of 105 compounds were identified, including 102 alkaloids, two phenolic acids, and one lactone compound. Liquid chromatography–mass spectrometry fingerprint method was established with ideal precision, stability and repeatability, and 12 quality differential markers were recognized between the above two herbs. Liquid chromatography–mass spectrometry method can be used for qualitative analysis of the constituents of Phellodendron amurense Rupr., providing reference for clarifying the material basis and promoting the clinical precision medication and quality evaluation of P. amurense Rupr.     

Speciation analysis of arsenic in prenatal and children's dietary supplements using microwave-enhanced extraction and ion chromatography–inductively coupled plasma mass spectrometry

A study was conducted to develop a microwave-enhanced extraction method for the determination of arsenic species in prenatal and children's dietary supplements prepared from plant materials. The method was optimized by evaluating the efficiency of various solutions previously used to extract arsenic from the types of plant materials used in the dietary supplement formulations. A multivitamin standard reference material (NIST SRM 3280) and a prenatal supplement sample were analyzed in the method optimization. The identified optimum conditions were 0.25 g of sample, 5 mL of 0.3 mol L⁻¹ orthophosphoric acid (H₃PO₄) and microwave heating at 90 °C for 30 min. The extracted arsenic was speciated by cation exchange ion chromatography–inductively coupled plasma mass spectrometry (IC–ICP-MS). The method detection limit (MDL) for the arsenic species was in the range 2–8 ng g⁻¹. Ten widely consumed prenatal and children's dietary supplements were analyzed using the optimized protocol. The supplements were found to have total arsenic in the concentration range 59–531 ng g⁻¹. The extraction procedure recovered 61–92% of the arsenic from the supplements. All the supplementary products were found to contain arsenite (As³⁺) and dimethylarsinic acid (DMA). Arsenate (As⁵⁺) was found in two of the supplements, and an unknown specie of arsenic was detected in one product. The results of the analysis were validated using mass balance by comparing the sum of the extracted and non-extracted arsenic with the total concentration of the element in the corresponding samples.     

Intensity of molecular ion peak in electron ionization mass spectra

Compounds from NIST??08 and Wiley 8th databases were considered as a representative subset of the general population of organic compounds which can be analyzed using mass spectrometry with electron ionization. The percentage of organic compounds as a function of intensity of molecular ion (M^+?) peak normalized to the base peak was determined for the first time. It was shown that only 26% compounds have high-intensity M^+? peaks (greater than 50% of base peak). Intensity of M^+? peak is less than or equal to 1 or 5% of base peak for 24 or 37% compounds respectively. It means that in case of trace-level analysis M^+? peak may not be registered for quarter (or even more) of organic compounds. It is well-known that the absence of M^+? peaks in electron ionization mass spectra reduces reliability of unknown compound identification based on library search. Therefore determination of molecular mass by independent technique (e.g., mass spectrometry with chemical ionization) is necessary for increasing the identification reliability.     

Design of guanidinium ionic liquid based microwave‐assisted extraction for the efficient extraction of Praeruptorin A from Radix peucedani

A series of novel tetramethylguanidinium ionic liquids and hexaalkylguanidinium ionic liquids have been synthesized based on 1,1,3,3‐tetramethylguanidine. The structures of the ionic liquids were confirmed by ¹H NMR spectroscopy and mass spectrometry. A green guanidinium ionic liquid based microwave‐assisted extraction method has been developed with these guanidinium ionic liquids for the effective extraction of Praeruptorin A from Radix peucedani. After extraction, reversed‐phase high‐performance liquid chromatography with UV detection was employed for the analysis of Praeruptorin A. Several significant operating parameters were systematically optimized by single‐factor and L₉ (3⁴) orthogonal array experiments. The amount of Praeruptorin A extracted by [1,1,3,3‐tetramethylguanidine]CH₂CH(OH)COOH is the highest, reaching 11.05 ± 0.13 mg/g. Guanidinium ionic liquid based microwave‐assisted extraction presents unique advantages in Praeruptorin A extraction compared with guanidinium ionic liquid based maceration extraction, guanidinium ionic liquid based heat reflux extraction and guanidinium ionic liquid based ultrasound‐assisted extraction. The precision, stability, and repeatability of the process were investigated. The mechanisms of guanidinium ionic liquid based microwave‐assisted extraction were researched by scanning electron microscopy and IR spectroscopy. All the results show that guanidinium ionic liquid based microwave‐assisted extraction has a huge potential in the extraction of bioactive compounds from complex samples.     

Simultaneous determination of anti‐diabetes/anti‐obesity drugs by LC/PDA,and targeted analysis of sibutramine analog in dietary supplements by LC/MS/MS

The safety of dietary supplements is questionable as there have been occasional reports of products contaminated with illegal adulterants. The present study was carried out to develop trustworthy methodologies to screen for six anti‐diabetic drugs (phenformin, rosiglitazone, glipizide, glimepiride, glybenclamide and gliclazide) and six anti‐obesity drugs (ephedrine, fenfluramine, T3, T4, fluoxetine and sibutramine) in dietary supplements. A simultaneous determination method of the 12 drugs by liquid chromatography coupled with a photodiode array (LC/PDA) was established and was validated for linearity (r² > 0.99), precision (RSD <13.3%), recoveries (88.8–115.9%) and reproducibility. Sibutramine and its analogs, N‐desmethylsibutramine, were subject to further investigation by LC/MS/MS because they were one of the major illegal adulterants. Our proposed method to monitor illegal drug adulterations in dietary supplements using LC/PDA is a simple and reliable, and therefore applicable to routine drug‐adulteration screening. Copyright © 2009 John Wiley & Sons, Ltd.     

Simultaneous analysis of 35 specific antihypertensive adulterants in dietary supplements using LC/MS/MS

A sensitive and specific LC/MS/MS method was developed for the simultaneous analysis of 35 compounds used for treating hypertension as adulterants in dietary supplements. The method was validated for specificity, linearity, accuracy, precision, limit of detection, limit of quantitation, stability and recovery. The limit of detection and limit of quantitation ranged from 0.20 to 20.0 and 0.50 to 60.0 ng/g, respectively. The linearity was good (r ² > 0.999), with intra‐ and interday precision levels of 0.43–7.87% and 0.65–9.95% and the intra‐ and interday accuracies of 84.36–115.82% and 83.78–118.69%, respectively. The stability (relative standard deviation) was <14.75%. The mean recovery was 80.81–117.86% (relative standard deviation <10.00%). Ninety‐seven commercial dietary supplements available in South Korea were analyzed. While none contained detectable amounts of the 35 antihypertensive compounds, the developed LC/MS/MS procedure can be used for routine analysis to monitor illegal adulteration in various forms of dietary supplements.     

Targeted and nontargeted screening and identification of 50 antihypertensive adulterants in dietary supplements and herbal medicines using quadrupole–orbitrap high resolution mass spectrometry with compound database

In the present work, a novel database of drug compounds and a rapid screening method based on ultra‐high performance liquid chromatography coupled to high resolution orbitrap mass spectrometry were developed and applied in the screening and identification of targeted and nontargeted antihypertensive adulterants in dietary supplements and herbal medicines. The established screening database includes retention time, exact mass, fragments, isotopic pattern, and MS² spectra library of the target compounds and thus provides automated search and identification of the targets with a single injection. The nontargeted compounds in the samples are identified through the full MS scan and MS² data by using the Chemspider database and the data analysis in XCalibur, MassFrontier and TraceFinder software. In addition, this method possesses excellent quantitative capacity. The novel approach was applied to 65 batches of samples that are claimed as “all‐natural” products having the antihypertensive function, among which nine batches were found to be positive. Multiple targeted and nontargeted antihypertensive adulterants were detected at levels ranging from 2.8 to 27.9 mg/g. The novel database and screening method demonstrated herein will be promising and powerful tools for rapid screening of antihypertensive adulterants in dietary supplements and herbal medicines.     

Structural determination by atmospheric pressure photoionization tandem mass spectrometry of some compounds isolated from the SARA fractions obtained from bitumen

We have identified compounds obtained from the SARA fractions of bitumen by using atmospheric pressure photoionization mass spectrometry and low‐energy collision tandem mass spectrometric analyses with a QqToF‐MS/MS hybrid instrument. The identified compounds were isolated from the maltene saturated oil and the aromatic fractions of the SARA components of a bitumen. The QqToF instrument had sufficient mass resolution to provide accurate molecular weight information and to enhance the tandem mass spectrometry results. The APPI‐QqToF‐MS analysis of the separated compounds showed a series of protonated molecules [M + H]⁺ and molecular ions [M]^+? of the same mass but having different chemical structures, in the maltene saturated oil and the aromatic SARA fractions. These isobaric ions were a molecular ion [M₂]^+? at m/z 418.2787 and a protonated molecule [M₅ + H]⁺ at m/z 287.1625 in the saturated oil fraction, and molecular ions [M₆]^+? at m/z 418.1584 and [M₇]^+? at m/z 287.1285 in the aromatic fraction. The identification of this series of chemical compounds was achieved by performing CID‐MS/MS analyses of the molecular ions [M]^+? ([M₁]^+? at m/z 446. 2980, [M₂]^+? at m/z 418.2787, [M₃]^+? at m/z 360.3350 and [M₄]^+? at m/z 346.2095) in the saturated oil fraction and of the [M₅ + H]⁺ ion at m/z 287.1625 also in the saturated oil fraction. The observed CID‐MS/MS fragmentation differences were explained by proposed different breakdown processes of the precursor ions. The presented tandem mass spectrometric study shows the capability of MS/MS experiments to differentiate between different classes of chemical compounds of the SARA components of bitumen and to explain the reasons for the observed mass spectrometric differences. However, greater mass resolution than that provided by the QqToF‐MS/MS instrument would be required for the analysis of the asphaltene fraction of bitumen. Copyright © 2011 John Wiley & Sons, Ltd.     

Signal losses in pesticide analysis using the broadband isolation waveform in a commercial quadrupole ion trap to accomplish precursor ion isolation in tandem mass spectrometry

Signal losses due to precursor ion isolation in a quadrupole-ion-trap mass spectrometer were studied using selected pesticides as model compounds. These signal losses originate from isolations of ion populations employing the broadband isolation (bbiso) waveform used in the Varian quadrupole ion-trap precursor ion isolation protocol. Signal losses were found to be ‘precursor ion structure’ dependent upon isolation using the bbiso. The effect of the bbiso waveform on the ionic structure and nature of substituents on the precursor ion was investigated. Isolation of old electron radical molecular ions of the type [M^+?] showed remarkable signal losses compared with isolation of fragment ions derived from the same compounds. The impact of the bbiso waveform on the response of the instrument using mass spectrometry/mass spectrometry and the bbiso waveform was also examined. The response of the instrument as related to the calculated Instrument Detection Limits was observed to parallel ion population losses.     

Development and evaluation of a high‐performance liquid chromatography/isotope ratio mass spectrometry methodology for δ13C analyses of amino sugars in soil

Amino sugars have been used as biomarkers to assess the relative contribution of dead microbial biomass of different functional groups of microorganisms to soil carbon pools. However, little is known about the dynamics of these compounds in soil. The isotopic composition of individual amino sugars can be used as a tool to determine the turnover of these compounds. Methods to determine the δ¹³C of amino sugars using gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) have been proposed in literature. However, due to derivatization, the uncertainty on the obtained δ¹³C is too high to be used for natural abundance studies. Therefore, a new high‐performance liquid chromatography/isotope ratio mass spectrometry (HPLC/IRMS) methodology, with increased accuracy and precision, has been developed. The repeatability on the obtained δ¹³C values when pure amino sugars were analyzed were not significantly concentration‐dependent as long as the injected amount was higher than 1.5 nmol. The δ¹³C value of the same amino sugar spiked to a soil deviated by only 0.3‰ from the theoretical value. Copyright © 2009 John Wiley & Sons, Ltd.     

Total and inorganic arsenic in dietary supplements based on herbs, other botanicals and algae—a possible contributor to inorganic arsenic exposure

The content of total and inorganic arsenic was determined in 16 dietary supplements based on herbs, other botanicals and algae purchased on the Danish market. The dietary supplements originated from various regions, including Asia, Europe and USA. The contents of total and inorganic arsenic was determined by inductively coupled plasma mass spectrometry (ICP-MS) and anion exchange HPLC-ICP-MS, respectively, were in the range of 0.58 to 5.0 mgkg^?1 and 0.03 to 3.2 mg?kg^?1, respectively, with a ratio between inorganic arsenic and total arsenic ranging between 5 and 100 %. Consumption of the recommended dose of the individual dietary supplement would lead to an exposure to inorganic arsenic within the range of 0.07 to 13 μg?day^?1. Such exposure from dietary supplements would in worst case constitute 62.4 % of the range of benchmark dose lower confidence limit values (BMDL₀₁ at 0.3 to 8 μg kg bw^?1 kg^?1 day^?1) put down by European Food Safety Authority (EFSA) in 2009, for cancers of the lung, skin and bladder, as well as skin lesions. Hence, the results demonstrate that consumption of certain dietary supplements could contribute significantly to the dietary exposure to inorganic arsenic at levels close to the toxicological limits established by EFSA.     

Targeted analysis of multiple pharmaceuticals,plant toxins and other secondary metabolites in herbal dietary supplements by ultra-high performance liquid chromatography–quadrupole-orbital ion trap mass spectrometry

In this study, an ultra-high performance liquid chromatography–quadrupole-orbital ion trap mass spectrometry (UHPLC–Q-orbitrap MS) method was developed and validated for simultaneous determination of 96 pharmaceuticals, plant toxins, and other plant secondary metabolites in herbal dietary supplements. Target analytes were extracted from samples using the QuEChERS (quick easy cheap effective rugged safe) procedure. The instrument was operated in full MS–data dependent tandem mass spectrometry (full MS–dd-MS/MS) acquisition mode which enabled collection of quantitative high resolution (HR) full mass spectral data and confirmatory HR MS/MS data in a single run. The method provided excellent selectivity in both full MS and dd-MS/MS mode. Under optimized collision energy settings, product ion spectra containing both precursor and two or more product ions were obtained for most of the analytes. Limits of detection (LODs) and limits of quantification (LOQs) for the method differed significantly for the examined matrices. LODs ≤ 10 μg kg⁻¹ and LOQs ≤ 50 μg kg⁻¹ were obtained for 48 to 81% of target compounds across five different matrices. With the exception of highly polar analytes, the optimized QuEChERS extraction procedure provided acceptable recoveries in the range 70%–120%. The precision of the method, characterized as the relative standard deviation (RSD, n = 5), was ≤25% and ≤18% at spiking concentrations of 50 μg kg⁻¹ and 500 μg kg⁻¹, respectively. Because of variations in matrix effects in extracts of herbal dietary supplements that differed in composition, the method of standard additions and an approach based on dilution of matrix components followed by quantification using solvent standards were applied for quantification. The procedure was used to examine commercial dietary supplements for the 96 analytes of interest. To the best of our knowledge, this is the first report of an integrated analysis and quantification of this wide range of compounds.     

Quantification of rosiglitazone in rat plasma and tissues via LC–MS/MS: Method development,validation, and application in pharmacokinetic and tissue distribution studies

A bioanalytical method for the quantification of rosiglitazone in rat plasma and tissues (adipose tissue, heart, brain, bone, and kidney) using LC–MS/MS was developed and validated. Chromatographic separation was achieved on a Gemini C₁₈ column (50 × 4.6 mm, 3 μm) using a mobile phase consisting of 10 mM ammonium formate (pH 4.0) and acetonitrile (10:90, v/v) at a flow rate of 0.8 mL/min and injection volume of 10 μL (internal standard: pioglitazone). LC–MS detection was performed with multiple reaction monitoring mode using target ions at m/z → 358.0 and m/z → 357.67 for rosiglitazone and pioglitazone (internal standard), respectively. The calibration curve showed a good correlation coefficient (r²) over the concentration range of 1–10,000 ng/mL. The mean percentage recoveries of rosiglitazone were found to be over the range of 92.54–96.64%, with detection and lower quantification limit of 0.6 and 1.0 ng/mL, respectively. The developed method was validated per U.S. Food and Drug Administration guidelines and successfully utilized to measure rosiglitazone in plasma and tissue samples. Further, the developed method can be utilized for validating specific organ-targeting delivery systems of rosiglitazone in addition to conventional dosage forms.     

Rapid determination of ginkgolic acids in Ginkgo biloba kernels and leaves by direct analysis in real time‐mass spectrometry

A novel method based on direct analysis in real time integrated with mass spectrometry was established and applied into rapid determination of ginkgolic acids in Ginkgo biloba kernels and leaves. Instrument parameter settings were optimized to obtain the sensitive and accurate determination of ginkgolic acids. At the sample introduction speed of 0.2 mm/s, high intensity of [M–H]^– ions for ginkgolic acids were observed in the negative ion mode by utilization of high‐purity helium gas at 450°C. Two microliters of methanol extract of G. biloba kernels or leaves dropped on the surface of Quick‐Strip module was analyzed after solvent evaporated to dryness. A series of standard solutions of ginkgolic acid 13:0 in the range of 2–50 mg/L were analyzed with a correlation coefficient r  = 0.9981 and relative standard deviation (n  = 5) from 12.5 to 13.7%. The limit of detection was 0.5 mg/L. The results of direct analysis in real time‐mass spectrometry were in agreement with those observed by thermochemolysis gas chromatography. The proposed method demonstrated significant potential in the application of the high‐throughput screening and rapid analysis for ginkgolic acids in dietary supplements.