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:
- Sharma et al. (2019) – ten-alkaloid UPLC–MS/MS plant/product QC
- King et al. (2020) – single-analyte plasma method
- Kamble et al. (2021) – 11-analyte plasma method (kratom tea & liquid shot)
- Manwill et al. (2022) – plant/product chemotype characterization (UPLC-HRMS)
- 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.
Figure C. Quantification workflow (plant/products)
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 Link:
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- U.S. Food and Drug Administration. (2018, May). Bioanalytical method validation: Guidance for industry. U.S. Food and Drug Administration.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.