Separation of Synephrine Enantiomers in Citrus Fruits by a Reversed Phase HPLC after Chiral Precolumn Derivatization

Tanaka, Sohei; Sekiguchi, Masaki; Yamamoto, Atsushi; Aizawa, Shiro; Sato, Kanta; Taga, Atsushi; Terashima, Hiroyuki; Ishihara, Yoshimi; Kodama, Shuji

doi:10.2116/analsci.18p441

Cited by 11 publications

(12 citation statements)

References 35 publications

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“…Although the content of synephrine did not change during drying, conversion between (R)synephrine and (S)-synephrine may occur at high temperatures. 33…”

Section: Hplc-pda Profile Of Seven Bioactive Components During Harvesting and Dryingmentioning

confidence: 99%

Evaluation of dynamic changes in the bioactive components in Citri Reticulatae Pericarpium (Citrus reticulata ‘Chachi’) under different harvesting and drying conditions

et al. 2020

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BACKGROUND: The Citrus reticulata 'Chachi' pericarp (CRCP) is one cultivar of Citri Reticulatae Pericarpium (Chenpi), which is widely applied in medicine and food. To determine the potential value of CRCP harvested at different stages and subjected to different drying processes, the dynamic changes in the bioactive components were profiled and evaluated in this study. RESULTS:The contents of all non-volatile components, i.e. synephrine, limonin, phenolic acids and flavonoids, decreased with delayed harvest time. The volatiles thujene, ⊍-pinene, ⊎-pinene, D-citronellol, D-citronellal, decanal, linalool, geraniol, L-cis-carveol, terpinen-4-ol, ⊍-terpineol, carvacrol, perillaldehyde, methyl 2-(methylamino)benzoate and D-limonene were considered the characteristic components for distinguishing CRCP harvested at different stages. Phenolic acids, synephrine and limonin were stable at different drying temperatures; however, high-temperature drying at 60°C induced a significant transformation in the flavonoids (especially polymethoxyflavones) and volatile substances in CRCP. CONCLUSIONS:The results suggested that most of the bioactive components declined with the growth of Citrus reticulata 'Chachi'. And it is believed that the fresh peel should be naturally sun-dried or dried at low temperature (30 or 45°C) rather than at high temperature (60°C) to prevent excessive loss of nutrients.

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“…Although the content of synephrine did not change during drying, conversion between (R)synephrine and (S)-synephrine may occur at high temperatures. 33…”

Section: Hplc-pda Profile Of Seven Bioactive Components During Harvesting and Dryingmentioning

confidence: 99%

Evaluation of dynamic changes in the bioactive components in Citri Reticulatae Pericarpium (Citrus reticulata ‘Chachi’) under different harvesting and drying conditions

et al. 2020

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“…1,7 Synephrine is an enantiomeric compound with the R-(−)-synephrine (l-enantiomer) predominantly found in the immature fruits, rinds and leaves of Citrus aurantium whereas the S-(+)-enantiomer (d-enantiomer) is found only in small quantities in ethanolic extracts of the fruit. 8 The two enantiomers have been reported to a percentage ratio of 92:8 (R-synephrine: S-synephrine). 8,9 Animal studies have suggested that the R-(−)-enantiomer is the more potent agonist on vascular α-, β 1 -and β 2 -adrenoceptors, 10 while S-(+)-synephrine has been suggested to block noradrenaline reuptake, 11 which may elevate blood pressure and heart rate.…”

Section: Introductionmentioning

confidence: 99%

“…8 The two enantiomers have been reported to a percentage ratio of 92:8 (R-synephrine: S-synephrine). 8,9 Animal studies have suggested that the R-(−)-enantiomer is the more potent agonist on vascular α-, β 1 -and β 2 -adrenoceptors, 10 while S-(+)-synephrine has been suggested to block noradrenaline reuptake, 11 which may elevate blood pressure and heart rate. There is a lack of human studies that investigate the stimulatory or sport performance effects synephrine enantiomers.…”

Section: Introductionmentioning

confidence: 99%

Racemic synephrine found in Citrus aurantium‐listing pre‐workout supplements suggests a non‐plant‐based origin

Koh

Chess-Williams

Lohning

2021

Drug Testing and Analysis

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Multi‐ingredient pre‐workout supplements (MIPS) contain Citrus aurantium as a source of bioactive amines such as p‐synephrine, but concerns regarding the authenticity of ingredients in some supplements as well as adverse effects from consumption have been raised. R‐(−)‐Synephrine is the predominant enantiomer in Citrus aurantium extracts while synthetic preparations are often racemic. The aims of this study were to develop a screening method to determine the ratio of synephrine enantiomers in pre‐workout supplements listing Citrus aurantium and to assess the ingredient authenticity by directly comparing their ratios to that found in Citrus aurantium standardised reference materials (SRMs). Quantification of enantiomers in the supplements and SRMs was achieved using a validated, high‐performance liquid chromatography‐single quadrupole mass spectrometry (HPLC‐UV‐QDa) direct enantioseparation method with a cellobiohydrolase (CBH) column (100 × 4.0 mm, 5 μM) and UV detection at 225 nm. Citrus aurantium SRMs were found to have an average enantiomeric ratio of 94:6 (R:S) with total synephrine ranging from 5.7 to 90.2 mg/g. Within the pilot sample of pre‐workout supplements tested, only 42% (5/12) had enantiomeric ratios consistent with the SRMs with total synephrine ranging from 0.03 to 91.2 mg/g. For the remaining supplements, four had racemic ratios of synephrine (0.14 to 5.4 mg/g), two lacked any detectable levels of synephrine, and one had solely the S‐(+)‐enantiomer (0.15 mg/g). These results bring the authenticity of labelling of some pre‐workout supplements into question and highlight the need for more stringent labelling regulations and testing for dietary supplements.

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“…Various isomeric forms of synephrine are reported in the literature, but there is now a consensus that p ‐synephrine is the only form present in bitter orange 12 . It was also reported that the ( R )‐ isomeric form is the primary form naturally present and any ( S )‐ isomers were the result of racemization induced by heat 13 …”

Section: Introductionmentioning

confidence: 99%

Analysis of bitter orange dietary supplements for natural and synthetic phenethylamines by LC–MS/MS

Pawar

Sagi

Leontyev

2020

Drug Testing and Analysis

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Citrus aurantium, commonly known as bitter orange, is a popular dietary supplement ingredient sold worldwide. Bitter orange supplements are sold primarily as weight management and sports performance products and have gained popularity after Ephedra products were banned from the US market. Supplements containing synephrine are reported to exhibit adverse cardiovascular effects especially in the presence of caffeine. In this study, an LC–MS/MS method was established to quantify five natural amines (synephrine, octopamine, tyramine, N‐methyltyramine, and hordenine) and four synthetic phenethylamines (phenylephrine, methylsynephrine, etilefrine, and isopropyloctopamine) in dietary supplements sold in the US. The method was validated and found to have acceptable performance to accurately measure analytes in complex botanical products. The average recoveries from a blank matrix were 88–125% with an RSD of 0.5–7.0%. Fifty‐nine products labeled to contain bitter orange peel, extract, or its amines were purchased and their amine content was measured. Several products were found to contain higher amounts of amines than that expected from a typical bitter orange extract. Of the 23 products that made label claims for synephrine, only 5 products (22%) were within 80–120% of labeled synephrine content. The presence of synthetic amines, methylsynephrine (up to 240 mg/daily serving), and isopropyloctopamine (up to 76 mg/daily serving), whose effects in humans are not known, were detected in six products and one product, respectively. While the use of methylsynephrine and isopropyloctopamine are not permitted in dietary supplements, hordenine, N‐methyltyramine, and octopamine are currently listed on the FDA's Dietary Supplement Ingredient Advisory List.

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Separation of Synephrine Enantiomers in Citrus Fruits by a Reversed Phase HPLC after Chiral Precolumn Derivatization

Cited by 11 publications

References 35 publications

Evaluation of dynamic changes in the bioactive components in Citri Reticulatae Pericarpium (Citrus reticulata ‘Chachi’) under different harvesting and drying conditions

Evaluation of dynamic changes in the bioactive components in Citri Reticulatae Pericarpium (Citrus reticulata ‘Chachi’) under different harvesting and drying conditions

Racemic synephrine found in Citrus aurantium‐listing pre‐workout supplements suggests a non‐plant‐based origin

Analysis of bitter orange dietary supplements for natural and synthetic phenethylamines by LC–MS/MS

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