The application of quantitative NMR for the facile, rapid and reliable determination of clindamycin phosphate in a conventional tablet formulation

Abstract

Spectroscopic tools such as NMR can be applied to the quantitative analysis of active pharmaceutical ingredients with relative ease and accuracy. Here, we demonstrate the quantification of clindamycin phosphate (CLP) in a conventional tablet formulation, performed using potassium hydrogen phthalate (KHP) as the internal standard and deuterium oxide (D2O) as the NMR solvent. The methyl protons signal of CLP at 0.72 ppm (triplet) relative to the signal of KHP at 7.37-7.40 ppm (multiplet) was used for quantification purposes using (1)H NMR. This method was shown to be specific and linear (r = 0.9997) within the CLP concentration range from 7.2 to 23.1 mg per 0.5 ml of D2O. The maximum relative standard deviation (RSD) of accuracy and precision was calculated at 0.39% and 0.64%, respectively. The limits of detection (LOD) and quantification were 0.04 and 0.11 mg/ml, respectively. The method was highly stable with a calculated RSD of 0.03%. The robustness of the method was demonstrated by changing four different parameters, and the difference among each parameter was ≤ 0.78%. The findings of this work were in good agreement with previously reported conventional HPLC-based approaches, highlighting its applicability in the determination of other active pharmaceutical ingredients in conventional formulations for quality control purposes.

Quantitation of memantine hydrochloride bulk drug and its tablet formulation using proton nuclear magnetic resonance spectrometry

“…From last four decades, several reports on qNMR have been published using 1 H, 13 C, 19 F, and 31 P NMR, each being extensively applied for drug quantification and validation. [18][19][20][21][22] To overcome hurdles associated with absence of absorptivity of MEM, we decided to develop a qNMR method without involvement of pre-column or post-column derivatization or any sample pretreatment. The method was extended to analysis of MEM in the marketed tablets.…”

Quantitative NMR Studies of Multiple Compound Mixtures

“…In order to secure the drug quality, 1 H qNMR is generally exploited for content determination of APIs, such as diquertin [167], iobitridol [171], and for quantitative analysis of excipients, such as lactose [179], pharmaceutical lipids [180], and 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) [181]. Liang et al [170] proposed a qNMR method for reliable content determination of clindamycin phosphate (CLP) tablets, which contained about 45% APIs. Aiming to demonstrate the capability of qNMR for low-content determination of a drug, Hou et al [169] developed a validated qNMR approach for quantification of avermectin B 1a (AVB 1a ) tablets, whose content was less than 5%.…”

Concentration Measurement of Amino Acid in Aqueous Solution by Quantitative 1H NMR Spectroscopy with Internal Standard Method

“…Recently, quantitative analysis using 1 H NMR spectroscopy has been reported. [1][2][3][4] The quantitative NMR technique uses a compound whose structure differs from the compound to be measured as a reference material. This method was examined as a new approach for rapid purity determination, and was eventually adopted for practical application.…”