Achiral liquid chromatography with circular dichroism detection for the determination of carnitine enantiomers in dietary supplements and pharmaceutical formulations

Andrés, Fernando de; Castañeda, Gregorio; Ríos, Ángel

doi:10.1016/j.jpba.2009.02.018

Cited by 23 publications

(8 citation statements)

References 34 publications

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“…Also, the published ECD spectrum is somewhat ambiguous, since it was measured with an HPLC-CD detector. 9 We decided then to repeat the measurements of the ECD spectra on a dedicated instrument. The results are given in Figure 5 for L-and D-acetyl carnitine in hydrochloride (3) (panel A) and zwitterionic forms (panel B), for L-and D-propyonil carnitine in hydrochloride form (2) (panel C), and for L-and D-carnitine in zwitterionic form (panel D).…”

Section: Resultsmentioning

confidence: 99%

“…Fast, accurate, and reproducible analytical methods capable to measure the enantiomeric excess of the final material are also highly desired 6 : in this field it is nice to acknowledge the seminal contribution of Professor Gasparrini and his group. 7,8 Carnitine and acyl carnitines being chiral molecules, optical rotation (OR) and circular dichroism in the UV range (electronic circular dichroism, ECD) were measured 9 ; in the latter case, ECD has been used as a detector of enantiomeric separation, down the line of HPLC separation protocol, without the accuracy required in a dedicated ECD experiment. To the best of our knowledge, though, no one has ever measured vibrational circular dichroism (VCD); yet various forms of vibrational spectroscopy, including IR, Raman, and SERS (surface-enhanced Raman spectroscopy) have been carried out and demonstrated to be useful.…”

Section: Abstract: Vibrational Circular Dichroism (Vcd); Carnitine; mentioning

confidence: 99%

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Vibrational Circular Dichroism (VCD) Reveals Subtle Conformational Aspects and Intermolecular Interactions in the Carnitine Family

et al. 2015

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Vibrational circular dichroism spectra (VCD) in the mid-IR region and electronic circular dichroism (ECD) spectra for three carnitine derivatives in the form of hydrochloride salts were recorded in deuterated methanol solutions. Density Functional Theory calculations help one to understand the significance of the observed VCD bands. VCD and ECD spectra are informative about the absolute configuration of the molecule, but VCD data reveal also some conformational aspects in the N,N,N-trimethyl moiety and inform us about intermolecular interactions gained from the carbonyl stretching region for the acyl substituted carnitines.

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Section: Resultsmentioning

confidence: 99%

Section: Abstract: Vibrational Circular Dichroism (Vcd); Carnitine; mentioning

confidence: 99%

Vibrational Circular Dichroism (VCD) Reveals Subtle Conformational Aspects and Intermolecular Interactions in the Carnitine Family

et al. 2015

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“…The best performing drug substances in this study had LOQs nearly equivalent to those of previous literature reports. Recall that these studies sought to optimize conditions favorable to CD detection rather than focus on compatibility with validated methods, and in doing so, were able to achieve LOQs around 0.5% [10,12,16,19]. The use of organic mobile phase components in the USP methods likely resulted in slightly poorer performance, but nevertheless, most LOQs were near this level.…”

Section: Resultsmentioning

confidence: 99%

Enantiomeric impurity analysis using circular dichroism spectroscopy with United States Pharmacopeia liquid chromatographic methods

Kirkpatrick

Fain

Yang

et al. 2018

Journal of Pharmaceutical and Biomedical Analysis

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Over 300 chiral drug substances lack official United States Pharmacopeia (USP) methods for the enantiomeric purity determination. Because enantiomeric analysis typically requires specialized methods for each drug compound, developing protocols for each of these 300+ substances would be an expensive and laborious endeavor. Alternatively, if a detector capable of determining the enantiomeric composition without chiral separation could be used with certain drug compounds, this could be implemented relatively rapidly into official testing monographs. Circular dichroism (CD) detection following HPLC (HPLC-CD) has been proposed for this purpose but studies performed thus far have not prioritized its compatibility with validated regulatory methods. In this study, HPLC-CD was evaluated for enantiomeric purity determinations of 13 drug substances using HPLC methods consistent with assay protocols described in United States Pharmacopeia (USP) monographs. Of these selected substances, three (sitagliptin, timolol, and levalbuterol) showed no CD activity and one other (levofloxacin) could not be analyzed due to incompatibility of the mobile phase with the CD detector. For the remaining 9 substances, method validation was performed to determine the linearity, accuracy, precision and limits of quantitation of enantiomer impurities, which was compared to limits established by USP. It was found that enantiomeric impurities for four substances (pramipexole, levocetirizine, (S)-citalopram, and tolterodine) could be quantitatively determined at levels suitable to USP specifications. This analysis demonstrated that HPLC-CD does provide an effective enantiomeric characterization strategy for compatible chiral compounds, and can be implemented quickly and economically compared to traditional column-dependent chiral separation or derivatization methods.

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“…Shell particles are a relatively recent trend in chromatographic separation, but several pharmaceutical-bioanalytical [105][106][107][108][109][110][111][112][113][114][115][116][117][118], food analytical [119][120][121][122][123][124][125][126][127][128][129], environmental [130][131][132][133][134] and multidimensional [135][136][137] separations can be found in the literature. Very recently, new commercially available wide-pore stationary phases demonstrate exceptional efficiency for protein separations [138][139][140].…”

Section: Superficially Porous Particlesmentioning

confidence: 99%

Evolution and Current Trends in Liquid and Supercritical Fluid Chromatography

Fekete¹,

Perrenoud²,

Guillarme

2014

CCHG

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Abstract:The current trend in high performance liquid chromatography (HPLC) tends toward the achievement of higher separation efficiency and shorter analysis time. Indeed, better performance in LC has become increasingly important in recent years mainly driven by the challenges of either analyzing more complex samples or increasing the numbers of samples per time unit. In the recent development of particle technology, the use of fully porous sub-2 m particles and sub-3 m shell particles have received considerable attention. Beside packed columns, the new generation of silica-based monolithic columns also offers very high separation power. However, to take full advantage of these innovative phases, the chromatographic system has also to be drastically optimized in terms of upper pressure limit and system volume.This revolution in column technology now spreads and covers several modes of liquid chromatography such as reversedphase liquid chromatography (RPLC), hydrophilic interaction liquid chromatography (HILIC), or even supercritical fluid chromatography (SFC). The HILIC and SFC, which can be considered as alternative modes of chromatography, could also be useful to extend the applicability of chromatography towards the analysis of very hydrophilic and lipophilic compounds, respectively.The present review gives an insight about the theory behind the success of current column technology and presents a summary of latest applications, using various modes of one-dimensional chromatography (RPLC, HILIC, SFC). This paper also shows that theoretically expected column efficiency could sometimes be compromised in practical work especially in the case of narrow bore columns.

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Achiral liquid chromatography with circular dichroism detection for the determination of carnitine enantiomers in dietary supplements and pharmaceutical formulations

Cited by 23 publications

References 34 publications

Vibrational Circular Dichroism (VCD) Reveals Subtle Conformational Aspects and Intermolecular Interactions in the Carnitine Family

Vibrational Circular Dichroism (VCD) Reveals Subtle Conformational Aspects and Intermolecular Interactions in the Carnitine Family

Enantiomeric impurity analysis using circular dichroism spectroscopy with United States Pharmacopeia liquid chromatographic methods

Evolution and Current Trends in Liquid and Supercritical Fluid Chromatography

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