Farquharson Amelia, Gladding Zachery, Ritchie Gary, Shende Chetan, Cosgrove Joseph, Smith Wayne, Brouillette Carl, Farquharson Stuart
Rennselaer Polytechnic Institute, Troy, NY 12180, USA.
Real-Time Analyzers, Inc., Middletown, CT 06457, USA.
Pharmaceutics. 2021 Feb 27;13(3):309. doi: 10.3390/pharmaceutics13030309.
Raman spectroscopy has proven valuable for determining the composition of manufactured drug products, as well as identifying counterfeit drugs. Here we present a simple method to determine the active pharmaceutical ingredient (API) mass percent in a sample that does not require knowledge of the identities or relative mass percents of the inactive pharmaceutical ingredients (excipients). And further, we demonstrated the ability of the method to pass or fail a manufactured drug product batch based on a calculated acceptance value in accordance with the US Pharmacopeia method for content uniformity. The method was developed by fitting the Raman spectra of 30 Claritin tablets with weighted percentages of the Raman spectrum of its API, loratadine, and a composite spectrum of the known excipients. The mean loratadine mass of 9.79 ± 40 mg per 100 mg tablet compared favorably to the 10.21 ± 0.63 mg per 100 mg tablet determined using high-performance liquid chromatography, both of which met the acceptance value to pass the 10 mg API product as labelled. The method was then applied to a generic version of the Claritin product that employed different excipients of unknown mass percents. A Raman spectrum representative of all excipients was created by subtracting the API Raman spectrum from the product spectrum. The Raman spectra of the 30 generic tablets were then fit with weighted percents of the pure loratadine spectrum and the created excipient spectrum, and used to determine a mean API mass for the tablets of 10.12 ± 40 mg, again meeting the acceptance value for the 10 mg API product. The data suggest that this simple method could be used to pass or fail manufactured drug product batches in accordance with the US Pharmacopeia method for content uniformity, without knowledge of the excipients.
拉曼光谱已被证明在确定制成药品的成分以及识别假药方面具有重要价值。在此，我们提出一种简单方法，用于测定样品中活性药物成分（API）的质量百分比，该方法无需了解非活性药物成分（辅料）的种类或相对质量百分比。此外，我们还证明了该方法能够根据美国药典含量均匀度方法计算出的验收值，判断制成药品批次是否合格。该方法是通过将30片氯雷他定片的拉曼光谱与API氯雷他定的拉曼光谱加权百分比以及已知辅料的复合光谱进行拟合而开发的。每100毫克片剂中氯雷他定的平均质量为9.79±40毫克，与使用高效液相色谱法测定的每100毫克片剂中10.21±0.63毫克相比，二者均符合验收值，能够通过标注为10毫克API的产品检测。然后，该方法被应用于氯雷他定产品的仿制药版本，该仿制药使用了质量百分比未知的不同辅料。通过从产品光谱中减去API拉曼光谱，创建了代表所有辅料的拉曼光谱。然后将30片仿制药片的拉曼光谱与纯氯雷他定光谱和创建的辅料光谱的加权百分比进行拟合，并用于确定片剂中API的平均质量为10.12±4毫克，同样符合10毫克API产品的验收值。数据表明，这种简单方法可用于根据美国药典含量均匀度方法判断制成药品批次是否合格，而无需了解辅料情况。
