Corynantheidine: Occurrence and Measurement

Corynantheidine : Occurence And Measurement

Occurrence & Quantification

Occurrence (concentration ranges) and quantification methods for corynantheidine in Mitragyna speciosa (kratom) leaves, extracts, and commercial products. Includes validated LC–MS/MS methods, detection/quantitation limits, and product-level surveys. No pharmacology here.

Primary Sources

Primary sources are method papers and analytical surveys with explicit numeric data and validation details. Key inclusions:

  1. Sharma et al. (2019) – ten-alkaloid UPLC–MS/MS plant/product QC
  2. King et al. (2020) – single-analyte plasma method
  3. Kamble et al. (2021) – 11-analyte plasma method (kratom tea & liquid shot)
  4. Manwill et al. (2022) – plant/product chemotype characterization (UPLC-HRMS)
  5. Large US product survey (2025) – quantified alkaloid content [1]

Data sources and inclusion criteria

Validated Methods

Validated analytical methods with run parameters, calibration ranges, and LLOQs [2].

Applied Surveys

Applied surveys reporting concentrations for leaves, extracts, teas, and commercial products [3].

Chemotype Context

Chemotype/variability context from product and plant studies [4].

Occurrence in leaves and extracts (validated LC–MS/MS)

Ten-Analyte UPLC–MS/MS Method

A ten-analyte UPLC–MS/MS method (triple quadrupole, ESI+, MRM) quantified key kratom indole/oxindole alkaloids across leaf extracts, alkaloid-rich fractions, lyophilized teas, and commercial products.

Reported Concentration Ranges (% w/w)
  • Mitragynine: 0.7–38.7%
  • Paynantheine: 0.3–12.8%
  • Speciociliatine: 0.4–12.3%
  • Speciogynine: 0.1–5.3%
  • Corynantheidine (minor set): 0.01–2.8%
    Minor set also included corynoxine, corynoxine B, isocorynantheidine, and 7-hydroxymitragynine
Analytical Details

BEH C18; mobile phase acetonitrile/10 mM ammonium acetate (pH 3.5); calibration 1–200 ng/mL; LLOQ 1 ng/mL; total run 22.5 min.

Occurrence in commercial products (capsules/powders/liquids)

US Product Survey

A US product survey (N = 341) reported alkaloid profiles consistent with kratom leaf, with no evidence of non-alkaloid adulterants. Minor alkaloids, including corynantheidine, had a mean content of 0.05% w/w across products analyzed [5].

Chemotype and Variability Context

UPLC-HRMS profiling of plants and products shows product-to-product variability and distinct chemotypes, affecting the relative abundance of major and minor alkaloids. (Corynantheidine was not a target in that HRMS panel, but the variability context is relevant.) [6]

Applied Matrices (Tea And Commercial Liquid) And Detection In Vivo

Plasma Pharmacokinetics

A validated 11-analyte plasma UPLC–MS/MS method (dynamic range 1–200 ng/mL, run time 11 min) quantified exposure after oral dosing of lyophilized kratom tea and a commercial liquid shot in rats. Among 11 alkaloids, corynantheidine showed systemic exposure (up to 8 h), confirming its presence in consumed products and detectability with validated MRM transitions [7].

Quantification methods (plant/products and bioanalysis)

A. Plant/Products QC (Ten-Alkaloid Panel)

Platform: UPLC–MS/MS (triple quad, ESI+, MRM)
Column: Waters ACQUITY BEH C18
Run: 22.5 min
Calibration: 1–200 ng/mL; LLOQ: 1 ng/mL
Matrices: leaf extracts, alkaloid-rich fractions, lyophilized teas, commercial products
Includes corynantheidine with chromatographic separation and MRM transitions demonstrated at the LLOQ [8].

B. Single-Analyte Plasma Method (Corynantheidine)

Platform: UPLC–MS/MS (ESI+, MRM 369.2→144.0/226.1)
Column: BEH C18 2.1 × 50 mm
Run: 3.0 min
Calibration: 1–500 ng/mL; sample volume: 25 µL; protein precipitation
Validated per FDA criteria (accuracy, precision, selectivity, recovery, stability) [9].

C. Multi-Analyte Plasma Method (11 Alkaloids)

Platform: UPLC–MS/MS (ESI+, MRM)
Run: 11 min
Calibration: 1–200 ng/mL
Applied to rat PK for lyophilized tea and a commercial liquid shot; corynantheidine quantified.

Reporting guidance for batch-level occurrence

Reporting Corynantheidine Content

When reporting corynantheidine content for products or plant material, include:

  • Matrix and preparation: leaf powder, extract, tea, etc., with extraction conditions.
  • Method: instrument model, column, gradient, MRM transitions, calibration range, LLOQ, and internal standard.
  • QC acceptance criteria: accuracy/precision aligned with the underlying validation [10].

Summary

Overview

Across leaves, extracts, and commercial products, corynantheidine is consistently a minor constituent, typically ≈0.01–2.8% w/w depending on matrix and batch [11]. An extensive U.S. market survey reports a mean of <0.05% w/w for this alkaloid in finished products [12].

Product-level quantification is supported by a validated ten-alkaloid UPLC–MS/MS QC method (ESI+, MRM; 1–200 ng/mL calibration; LLOQ 1 ng/mL; ~22.5 min run) [13]. In vivo detectability is established by two plasma methods: a single-analyte UPLC–MS/MS for corynantheidine (MRM 369.2→144.0/226.1; 1–500 ng/mL; 3.0 min run) [14], and a validated 11-analyte plasma panel (1–200 ng/mL; ~11 min) applied to kratom tea and a commercial liquid shot [15].

Reported product-to-product variability/chemotypes further explain differences in minor-alkaloid levels across samples [16]. Together, these data and methods provide a reproducible framework for batch-level occurrence reporting (matrix, method, calibration/LLOQ, internal standard) and enable cross-study comparisons of corynantheidine content in kratom materials and products.

Reference

  1. Sharma, A., Kamble, S. H., León, F., Chear, N. J.-Y., King, T. I., Berthold, E. C., … Avery, B. A. (2025). Chemical analysis and alkaloid intake for kratom products available in the United States. Drug Testing and Analysis.
  2. King, T. I., Sharma, A., Kamble, S. H., León, F., Berthold, E. C., Popa, R., … Avery, B. A. (2020). Bioanalytical method development and validation of corynantheidine, a kratom alkaloid, using UPLC–MS/MS, and its application to preclinical pharmacokinetic studies. Journal of Pharmaceutical and Biomedical Analysis, 180, 113019.
  3. Sharma, A., Kamble, S. H., León, F., Chear, N. J.-Y., King, T. I., Berthold, E. C., … Avery, B. A. (2019). Simultaneous quantification of ten key Mitragyna speciosa (kratom) alkaloids in leaf extracts and commercial products by UPLC–MS/MS. Drug Testing and Analysis, 11(8), 1162–1171.
  4. Manwill, P. K., Flores-Bocanegra, L., Khin, M., Raja, H. A., Cech, N. B., Oberlies, N. H., & Todd, D. A. (2022). Kratom (Mitragyna speciosa) validation: Quantitative analysis of indole and oxindole alkaloids reveals chemotypes of plants and products. Planta Medica, 88(9–10), 838–857.
  5. Sharma, A., Kamble, S. H., León, F., Chear, N. J.-Y., King, T. I., Berthold, E. C., … Avery, B. A. (2025). Chemical analysis and alkaloid intake for kratom products available in the United States. Drug Testing and Analysis.
  6. Manwill, P. K., Flores-Bocanegra, L., Khin, M., Raja, H. A., Cech, N. B., Oberlies, N. H., & Todd, D. A. (2022). Kratom (Mitragyna speciosa) validation: Quantitative analysis of indole and oxindole alkaloids reveals chemotypes of plants and products. Planta Medica, 88(9–10), 838–857.
  7. Kamble, S. H., Berthold, E. C., King, T. I., Kanumuri, S. R. R., Popa, R., Herting, J. R., … McCurdy, C. R. (2021). Pharmacokinetics of eleven kratom alkaloids following an oral dose of either traditional or commercial kratom products in rats. Journal of Natural Products, 84(4), 1104–1112.
  8. Sharma, A., Kamble, S. H., León, F., Chear, N. J.-Y., King, T. I., Berthold, E. C., … Avery, B. A. (2019). Simultaneous quantification of ten key Mitragyna speciosa (kratom) alkaloids in leaf extracts and commercial products by UPLC–MS/MS. Drug Testing and Analysis, 11(8), 1162–1171.
  9. King, T. I., Sharma, A., Kamble, S. H., León, F., Berthold, E. C., Popa, R., … Avery, B. A. (2020). Bioanalytical method development and validation of corynantheidine… Journal of Pharmaceutical and Biomedical Analysis, 180, 113019.
  10. U.S. Food and Drug Administration. (2018, May). Bioanalytical method validation: Guidance for industry. U.S. Food and Drug Administration.
  11. Sharma, A., Kamble, S. H., León, F., Chear, N. J.-Y., King, T. I., Berthold, E. C., … Avery, B. A. (2019). Simultaneous quantification of ten key Mitragyna speciosa (kratom) alkaloids in leaf extracts and commercial products by UPLC–MS/MS. Drug Testing and Analysis, 11(8), 1162–1171.
  12. Sharma, A., Kamble, S. H., León, F., Chear, N. J.-Y., King, T. I., Berthold, E. C., … Avery, B. A. (2025). Chemical analysis and alkaloid intake for kratom products available in the United States. Drug Testing and Analysis.
  13. Sharma, A., Kamble, S. H., León, F., Chear, N. J.-Y., King, T. I., Berthold, E. C., … Avery, B. A. (2019). Simultaneous quantification of ten key Mitragyna speciosa (kratom) alkaloids in leaf extracts and commercial products by UPLC–MS/MS. Drug Testing and Analysis, 11(8), 1162–1171.
  14. King, T. I., Sharma, A., Kamble, S. H., León, F., Berthold, E. C., Popa, R., … Avery, B. A. (2020). Bioanalytical method development and validation of corynantheidine… Journal of Pharmaceutical and Biomedical Analysis, 180, 113019.
  15. Kamble, S. H., Berthold, E. C., King, T. I., Kanumuri, S. R. R., Popa, R., Herting, J. R., … McCurdy, C. R. (2021). Pharmacokinetics of eleven kratom alkaloids… Journal of Natural Products, 84(4), 1104–1112.
  16. Manwill, P. K., Flores-Bocanegra, L., Khin, M., Raja, H. A., Cech, N. B., Oberlies, N. H., & Todd, D. A. (2022). Kratom (Mitragyna speciosa) validation: Quantitative analysis of indole and oxindole alkaloids reveals chemotypes of plants and products. Planta Medica, 88(9–10), 838–857.