Figure 1 (TOC) is an example of a 30-day measurement-system equivalancy test protocol from a pharmaceutical company. In this
protocol, the statistical parmameters of mean and standard deviation represent data-quality equivalency. The mean is determined
from repeated measurements of the process. This average includes contributions from the pharmaceutical water itself, the sampling
process, and the inherent accuracy of the measurement device. By pairing the on-line and laboratory data collection, the process
water variability remains common between the two systems. In addition, the inherent accuracy of the instruments remains common,
based on previous method validation results. The mean serves to quantify the added TOC contributions of the sampling process
itself. Additionally, the standard deviation is used to assess the repeatability of the measurement system, taking into account
the variation of the sampling process and the measurement device.
Figure 1 (TOC): A 30-day measurement-system equivalency test of off-line and on-line total organic carbon (TOC) analysis.
(FIGURE 1 (TOC) IS COURTESY OF GE Analytical Instruments)
TOC section reference
1. FDA, Guidance for Industry: PAT (Rockville, MD, 2004).
Ultra-fast liquid chromatography
Simon Robinson, HPLC product manager, Shimadzu Scientific Instruments (Columbia, MD)
Over-the-counter cold medicines often contain multiple active ingredients. These actives include combinations of decongestants,
antihistamines, pain relievers, cough suppressants, and expectorants in addition to numerous vitamins and herbal extracts—all
of which exhibit different chemical properties. A wide range of analyte polarities often makes developing chromatographic
methods challenging. Separating ingredients in a cold medicine is important to understand the content of each medication and
product quality. A high-speed liquid chromatographic system (Prominence UFLCxr with a SPD-M20A photodiode array detector,
Shimazdu Scientific Instruments) was used to analyzed 20 common cold medcines.
A standard mixture of cold-medicine ingredients was prepared (dissolving them in Mobile Phase A/acetonitrile = 1/1 (v/v),
100 mg/L, each) and analyzed using the conditions shown in Table I (UF LC). The mixture consisted of thiamine, acetaminophen,
caffeine, riboflavin, hesperidin, ethenzamide, chlorpheniramine, ambroxol, noscapine, isopropamide, ispropylantipyrine, dextromethorphan,
glycyrrhizin, bromhexine, clemastine, and ibruprofen. The contents of a capsule of cold medicine was dissolved in 100 mL of
Mobile Phase A/acetonitrile = 1/1 (v/v), or in the case of tablet form, a single tablet was dissolved in 50 mL of the previously
described mobile-phase acetonitrile solution. The resultant solution was passed through a 0.22 µm pore membrane filter and
analyzed using the conditions in Table I (UFLC).
Figure 1 (UFLC): Results of five serial ultra-high-speed liquid chromatographic analyses. (FIGURE 1 (UFLC) IS COURTESY OF
SHIMAZDU SCIENTIFIC INSTRUMENTS)