HPLC resolution using polysaccharide derivatives as CSP

Yamamoto, Chiyo

doi:10.1016/b978-044451669-5/50007-7

Cited by 2 publications

(2 citation statements)

References 109 publications

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“…Single enantiomer drugs make up a large and growing portion of over-the-counter and prescription drug products, and in some cases offer improved efficacy compared to racemic alternatives [1–6]. Unfortunately, traditional analysis methods for determining drug substance impurities, such as high-performance liquid chromatography (HPLC), are not suitable for chiral analysis without specialization because opposite enantiomers typically require a specific chiral stationary phase or mobile phase additive to separate enantiomers prior to detection [7,8]. As a result, unique methods must be developed to determine the enantiomeric purity for different compounds.…”

Section: Introductionmentioning

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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Section: Introductionmentioning

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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“…Chiral molecules are typically analyzed either by some type of chiroptical method such as polarimetry, 1,2 Raman optical activity, 3,4 or electronic 5,6 and vibrational circular dichroism, 7,8 or by chromatography or capillary electrophoresis in which some type of chiral auxiliary is employed. [9][10][11][12][13][14][15][16] Chiroptical instrumentation is often expensive, especially if continuous wavelengths are monitored, and the use of chiral auxiliaries may involve separation times of 10 or more minutes per sample prior to analysis.…”

Section: Introductionmentioning

confidence: 99%

Novel Spectropolarimeter Employing Fixed Polarizers for the Determination of Optically Active Samples

et al. 2008

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A novel spectropolarimeter, based on modification of an ordinary, inexpensive, multiwavelength ultraviolet (UV)-visible-near-infrared (NIR) spectrophotometer, is described and applied to the determination of sucrose, sucrose inversion, and enantiomeric composition of solutions of (R)-(+)-limonene and (S)-(-)-limonene. The instrument has no moving parts, and optical rotation measurements are encoded as an apparent absorbance. Apparent absorbance measurements can be combined with multivariate statistical analysis over a wide spectral range, and a background correction technique that employs the sample as its own blank provides an effective means of correcting for the presence of chromophores that also absorb over the wavelengths of interest. The instrument was tested against an ordinary polarimeter and showed good performance with both colorless and colored samples.

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HPLC resolution using polysaccharide derivatives as CSP

Cited by 2 publications

References 109 publications

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

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

Novel Spectropolarimeter Employing Fixed Polarizers for the Determination of Optically Active Samples

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