Development and Validation of 2-Azaspiro [4,5] Decan-3-One (Impurity A) in Gabapentin Determination Method Using qNMR Spectroscopy.

Nataliya E Kuz’Mina,Anna I Lutceva,Mikhail D Khorolskiy,Sergey V Moiseev

doi:10.3390/molecules26061656

Nataliya E Kuz’Mina, Anna I Lutceva + Show 2 more

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https://doi.org/10.3390/molecules26061656

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Abstract

The authors developed a 1H qNMR test procedure for identification and quantification of impurity A present in gabapentin active pharmaceutical ingredient (API) and gabapentin products. The validation studies helped to determine the limit of quantitation and assess linearity, accuracy, repeatability, intermediate precision, specificity, and robustness of the procedure. Spike-and-recovery assays were used to calculate standard deviations, coefficients of variation, confidence intervals, bias, Fisher’s F test, and Student’s t-test for assay results. The obtained statistical values satisfy the acceptance criteria for the validation parameters. The authors compared the results of impurity A quantification in gabapentin APIs and capsules by using the 1H qNMR and HPLC test methods.

Highlights

Gabapentin (2-[1-(aminomethyl) cyclohexyl] acetic acid) is a synthetic and nonbenzodiazepine analogue of γ-aminobutyric acid
The validation studies helped to determine the limit of quantitation and assess linearity, accuracy, repeatability, intermediate precision, specificity, and robustness of the procedure
The authors compared the results of impurity A quantification in gabapentin active pharmaceutical ingredient (API) and capsules by using the 1H qNMR and HPLC test methods

Summary

Introduction

Gabapentin (2-[1-(aminomethyl) cyclohexyl] acetic acid) is a synthetic and nonbenzodiazepine analogue of γ-aminobutyric acid. HPLC determination of ImpA requires generation of a calibration curve using a pharmacopoeial reference standard for ImpA (which accounts for the relative nature of measurements). QNMR is considered as an absolute method for measuring the molar ratio of the analytes in a test sample, as well as the weight content of one component relative to another component, because the functional relationships between the analytes and the measurands (integrated intensities) are well-known: the molar ratio of the components in a mixture is equal to the ratio of the normalized integrated intensities of the signals of these components. QNMR quantification of an impurity relative to the main component is considered a direct method because of the direct measurement of the ratio of integrated intensities of the main component and impurity signals.

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