Synthesis, characterization, method development, and validation of nor‐ethylmorphine hydrochloride reference material using established analytical techniques for dope control analysis

Pawar, Sachin Dattram; Kumar, Gangasani Jagadeesh; Chikkondra, Aruna; Lal, Banwari; Radhakrishnanand, P.; Murty, Upadhyayula Suryanarayana; Sahu, Puran Lal; Dubey, Sachin; Soni, Arpit; Kumar, Pramod

doi:10.1002/dta.3178

Cited by 5 publications

(3 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2.4 | RP-HPLC method development, validation, and purity analysis [1][2][3]5,[12][13][14][15][16][17] Purity analysis of reference material is always of paramount importance. HPLC analysis has been considered one of the best reliable, cheaper, and robust techniques for purity analysis.…”

Section: Characterization Of Carboxy Toremifene Using Nmr Hrms Ft-ir ...mentioning

confidence: 99%

Process development for the total synthesis of the novel drug metabolite Carboxy toremifene as a standard reference material along with characterization and purity assessment for the Antidoping quality Control Purposes

Kumar

Pawar

et al. 2022

Drug Testing and Analysis

Self Cite

View full text Add to dashboard Cite

Tamoxifen and toremifene are two selective estrogen receptor modulators (SERMs) commonly used to treat breast cancer in women. Toremifene is well‐known as a triphenylethylene derivative. Carboxy toremifene is a common metabolite of toremifene and tamoxifen. Since 2005, the World Anti‐Doping Agency (WADA) has banned the SERMs category during in and out of competition. These substances are in the S4 category in the WADA prohibited list as “agents with anti‐oestrogenic activity.” However, there is no commercially accessible carboxy toremifene reference material in the market. This research highlights the novel synthetic procedure, the development of a carboxy toremifene HPLC method, and validation, along with detailed characterization using advanced analytical techniques using 1H NMR, HRMS, FT‐IR‐ATR and UV–visible spectroscopy. RP‐HPLC‐DAD method was developed and validated to assess the purity of carboxy toremifene. Developed reference material has shown 100% purity. Therefore, we recommend that this synthesized carboxy toremifene may be used as reference material to strengthen the WADA‐accredited lab to maintain a clean sports mission during sports competitions.

show abstract

Section: Characterization Of Carboxy Toremifene Using Nmr Hrms Ft-ir ...mentioning

confidence: 99%

Process development for the total synthesis of the novel drug metabolite Carboxy toremifene as a standard reference material along with characterization and purity assessment for the Antidoping quality Control Purposes

Kumar

Pawar

et al. 2022

Drug Testing and Analysis

Self Cite

View full text Add to dashboard Cite

show abstract

“…As a pervasive phenomenon in nature, chirality refers to the property of two enantiomeric molecules having the same structural formula but being nonsuperimposable in their spatial arrangement (Pawar et al., 2022). Enantiomers possess identical physical and chemical properties while exhibiting different biological activities, including the potential for divergent effects or toxicity (Ballard et al., 2019; Liu et al., 2022).…”

Section: Introductionmentioning

confidence: 99%

Study on the stability of molecular chirality and the configuration protection of dihydromyricetin in vine tea

Li,

Sha,

Sun

et al. 2024

Journal of Food Science

View full text Add to dashboard Cite

This study aims to investigate the impact of four key factors, namely, temperature, water source, metal ion, and pH, on the stability of molecular chirality of dihydromyricetin (DMY) and proposed effective strategies for configuration protection. The findings reveal that temperatures exceeding 80°C could accelerate the racemization process of DMY, with a significant increase in racemization observed at 100°C. In addition, DMY exhibited heightened stability in ultrapure water as compared to various water sources, including pure water‐1, pure water‐2, mineral water, and running water. Notably, the presence of Fe2+ displayed an inhibitory effect on the racemization of DMY, whereas Mg2+, Ca2+, and Mn2+ showed a substantial promotional effect. Additionally, acidic conditions (pH < 5.0) were found to be protective for maintaining the stability of DMY, whereas alkaline conditions (pH > 9.0) were observed to be detrimental. Meanwhile, we first identified the presence of another pair of DMY isomers in this work.

show abstract

“…23,24 Previously, our laboratory has synthesized three different reference materials, carboxytoremifene, para-hydroxyprenylamine and norethylmorphine, and supplied them to NDTL for further supply to WADAaccredited laboratories for routine QAQC use. [25][26][27][28][29] However, reference materials of the target metabolites are required for calibration of test results and confirmation of dope control methods, simplifying the metabolic assessment of prohibited drugs. 30 As such, it was proposed to develop efficient synthetic routes for highly purified reference materials of OS, NS and ES (as shown in Figure 1), which are prohibited in sports by WADA under the S6 stimulant category for anti-doping studies.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of octopamine sulfate, norfenefrine sulfate and etilefrine sulfate reference materials for doping control

Kalita,

Pawar,

Vernekar

et al. 2023

J of Chemical Tech & Biotech

Self Cite

View full text Add to dashboard Cite

BACKGROUND: Doping is the use of prohibited substances by athletes to improve their performance. World Anti-Doping Agency (WADA)-accredited laboratories require various metabolite reference standards of the prohibited chemical substances or drugs for routine quality control. Therefore, it was proposed to develop efficient synthetic methodologies for highly pure reference materials of Phase II metabolites of octopamine, norfenefrine and etilefrine, which are prohibited in sports by WADA under the S6 stimulant category. The reference materials were characterized using various analytical techniques. New highperformance liquid chromatography with diode-array detection (HPLC-DAD) methods were developed for purity assessment.RESULTS: The synthesized Phase II metabolite reference standards, i.e. octopamine sulfate, norfenefrine sulfate and etilefrine sulfate, were confirmed by 1 H NMR, 13 C NMR, liquid chromatography-high-resolution mass spectrometry (LC-HRMS), attenuated total reflectance Fourier transform infrared and thermogravimetric analysis. In the LC-HRMS study, the mass error value of synthesized compounds was less than 10 ppm (error) which confirms the identity of the reference materials. New HPLC-DAD method were developed to ensure the purity of the reference materials. We used the HILIC column as metabolite reference standards are highly polar. The mobile phase was composed of water and acetonitrile in fixed composition. The HPLC-DAD purity of the developed reference materials was observed as 100%.CONCLUSION: We have developed reproducible synthetic routes for octopamine sulfate, norfenefrine sulfate and etilefrine sulfate, which are prohibited in sports by WADA. The synthesized metabolites were characterized using different advanced analytical techniques. These reference standards will be helpful to all WADA-accredited laboratories in routine anti-doping testing.

show abstract

Synthesis, characterization, method development, and validation of nor‐ethylmorphine hydrochloride reference material using established analytical techniques for dope control analysis

Cited by 5 publications

References 16 publications

Process development for the total synthesis of the novel drug metabolite Carboxy toremifene as a standard reference material along with characterization and purity assessment for the Antidoping quality Control Purposes

Process development for the total synthesis of the novel drug metabolite Carboxy toremifene as a standard reference material along with characterization and purity assessment for the Antidoping quality Control Purposes

Study on the stability of molecular chirality and the configuration protection of dihydromyricetin in vine tea

Synthesis and characterization of octopamine sulfate, norfenefrine sulfate and etilefrine sulfate reference materials for doping control

Contact Info

Product

Resources

About