Isotopic 13C NMR spectrometry to assess counterfeiting of active pharmaceutical ingredients: Site-specific 13C content of aspirin and paracetamol

Silvestre, Virginie; Mboula, Vanessa Maroga; Jouitteau, Catherine; Akoka, Serge; Robins, Richard J.; Remaud, Gérald S.

doi:10.1016/j.jpba.2009.04.030

Cited by 85 publications

(98 citation statements)

References 25 publications

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“…Spectra were obtained with a signal-to-noise ratio of ∼650, from which the distribution of 13 C at each carbon position, the reduced molar fraction f i /F i , was calculated from the areas under the peaks. This was then converted to δ 13 C i (‰) values using the δ 13 C g (‰) obtained by irm-MS (Table 1), as previously described (10,19).…”

Section: Resultsmentioning

confidence: 99%

“…Purification including a final crystallization from aqueous acetone yielded pure [>99.5% (wt/wt)] tramadol. Irm-13 C NMR spectra were acquired using 200 mg of pure tramadol from the field collection in slightly aqueous acetone and the δ 13 C i (‰) values computed as described above (10,19).…”

Section: Resultsmentioning

confidence: 99%

“…must be the attenuated and superficial manifestations of isotopic differences within molecules" (18). Only recently, however, has it become possible to access these intramolecular distributions of 13 C in whole molecules through the power of irm-13 C NMR at natural abundance to give direct measurement of position-specific 13 C/ 12 C ratios and to obtain quantification of all individual isotopomers (19). This technique has been exploited in authenticity and in examining differences in fermentation pathways.…”

Section: Significancementioning

confidence: 99%

“…The curve fitting was carried out with a Lorentzian mathematical model using Perch Software (Perch NMR Software; University of Kuopio, Kuopio, Finland). Data were processed as described previously, and the δ 13 C i (‰) values were calculated from the reduced molar fraction f i /F i and the δ 13 C g (‰) obtained by isotope ratio measurement by mass spectrometry (10,19).…”

Section: H Nmrmentioning

confidence: 99%

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A retro-biosynthetic approach to the prediction of biosynthetic pathways from position-specific isotope analysis as shown for tramadol

Romek

Nun

Remaud

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Tramadol, previously only known as a synthetic analgesic, has now been found in the bark and wood of roots of the African medicinal tree Nauclea latifolia. At present, no direct evidence is available as to the biosynthetic pathway of its unusual skeleton. To provide guidance as to possible biosynthetic precursors, we have adopted a novel approach of retro-biosynthesis based on the position-specific distribution of isotopes in the extracted compound. Relatively recent developments in isotope ratio monitoring by 13 C NMR spectrometry make possible the measurement of the nonstatistical position-specific natural abundance distribution of 13 C (δ 13 C i ) within the molecule with better than 1‰ precision. Very substantial variation in the 13 C positional distribution is found: between δ 13 C i = −11 and −53‰. Distribution is not random and it is argued that the pattern observed can substantially be interpreted in relation to known causes of isotope fractionation in natural products. Thus, a plausible biosynthetic scheme based on sound biosynthetic principals of precursorsubstrate relationships can be proposed. In addition, data obtained from the 18 O/ 16 O ratios in the oxygen atoms of the compound add support to the deductions made from the carbon isotope analysis. This paper shows how the use of 13 C NMR at natural abundance can help with proposing a biosynthetic route to compounds newly found in nature or those difficult to tackle by conventional means.NMR spectrometry | position-specific isotope analysis | retro-biosynthesis | tramadol | Nauclea latifolia

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

Section: H Nmrmentioning

confidence: 99%

See 2 more Smart Citations

A retro-biosynthetic approach to the prediction of biosynthetic pathways from position-specific isotope analysis as shown for tramadol

Romek

Nun

Remaud

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Several studies have reported the use of spectroscopic fingerprints provided by nuclear magnetic resonance (NMR) [6][7][8], near infrared spectroscopy (NIR) [9][10][11] and Fourier transform infrared spectroscopy (FT-IR) [12,13] in the field of quality control and/or discrimination of food origin. The main drawback of these techniques is their complexity of interpretation.…”

Section: Introductionmentioning

confidence: 99%

Impurity fingerprints for the identification of counterfeit medicines—A feasibility study

Sacré

Deconinck

Daszykowski

et al. 2011

Analytica Chimica Acta

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Most of the counterfeit medicines are manufactured in non good manufacturing practices (GMP) conditions by uncontrolled or street laboratories. Their chemical composition and purity of raw materials may, therefore, change in the course of time. The public health problem of counterfeit drugs is mostly due to this qualitative and quantitative variability in their formulation and impurity profiles.In this study, impurity profiles were treated like fingerprints representing the quality of the samples. A total of 73 samples of counterfeit and imitations of Viagra ® and 44 samples of counterfeit and imitations of Cialis ® were analysed on a HPLC-UV system. A clear distinction has been obtained between genuine and illegal tablets by the mean of a discriminant partial least squares analysis of the log transformed chromatograms. Following exploratory analysis of the data, two classification algorithms were applied and compared. In our study, the knearest neighbour classifier offered the best performance in terms of correct classification rate obtained with cross-validation and during external validation. For Viagra ® , both crossvalidation and external validation sets returned a 100% correct classification rate. For Cialis ® 92.3% and 100% correct classification rates were obtained from cross-validation and external validation, respectively.

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Analysis of Counterfeit Medicines and Adulterated Dietary Supplements by NMR

Malet‐Martino

Martino

2015

eMagRes

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Isotopic 13C NMR spectrometry to assess counterfeiting of active pharmaceutical ingredients: Site-specific 13C content of aspirin and paracetamol

Cited by 85 publications

References 25 publications

A retro-biosynthetic approach to the prediction of biosynthetic pathways from position-specific isotope analysis as shown for tramadol

A retro-biosynthetic approach to the prediction of biosynthetic pathways from position-specific isotope analysis as shown for tramadol

Impurity fingerprints for the identification of counterfeit medicines—A feasibility study

Analysis of Counterfeit Medicines and Adulterated Dietary Supplements by NMR

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