Pharmaceutical analysis methods

Detection If a small capillary diameter is desired for efficiency purposes, the detection part of the capillary can be adapted for better detection sensitivity. Examples are the bubble cell capillary and the Z-cell. In the bubble cell capillary, the capillary diameter is enlarged at the detection window so that better concentration sensitivity is obtained. If you implement a bubble cell capillary in your pharmaceutical analysis method, it is important to test different batches. Test also whether you need a bubble cell capillary or whether you can gain similar sensitivity increase with a proper injection procedure. Also, check the effect of the bubble cell on band broadening. An approximately three-times sensitivity enhancement is possible. 

Box 1.1 Questions pharmaceutical analysis methods are used to answer... 

The nine strategies form a powerful set of tools to devise, construct, and refine pharmaceutical analysis methods. The proactive use of a single strategy, or the combination of several, produces unique information and inspires new perspectives on analysis. In this way, analysis methods create new mechanisms for information gathering, rather than passively waiting for a sample to be generated. And in this way LC/MS analysis capabilities partnered with samplegenerating disciplines to create new accelerated development opportunities. 

Howard, B. Experiences and expectations for transferring automated pharmaceutical analysis methods in a global pharmaceutical company. In Proceedings of the 1999 International Symposium on Laboratory Automation and Robotics, CD-ROM version, ISLAR, Hopkinton, MA, 1999. 

Table 9.4. Validation Requirements for Each Type of Pharmaceutical Analysis Method...

The reader is also referred to Chapter 6 on parameters and acceptance criteria for the validation of various pharmaceutical analysis methods. 

KD Altria. Application of capillary electrophoresis to pharmaceutical analysis. Methods Mol Biol 52 265-284, 1996. 

Marsh A, Broderick M, Altria K, Power J, Donegan S, Clark B. Capillary electrophoresis for pharmaceutical analysis. Methods Mol. Biol 2008 384 205 245. 

However, compared with the traditional analytical methods, the adoption of chromatographic methods represented a signihcant improvement in pharmaceutical analysis. This was because chromatographic methods had the advantages of method specihcity, the ability to separate and detect low-level impurities. Specihcity is especially important for methods intended for early-phase drug development when the chemical and physical properties of the active pharmaceutical ingredient (API) are not fully understood and the synthetic processes are not fully developed. Therefore the assurance of safety in clinical trials of an API relies heavily on the ability of analytical methods to detect and quantitate unknown impurities that may pose safety concerns. This task was not easily performed or simply could not be carried out by classic wet chemistry methods. Therefore, slowly, HPLC and GC established their places as the mainstream analytical methods in pharmaceutical analysis. 

In pharmaceutical analysis the detection of impurities under a chromatographic peak is a major issue. An important step forward in the assessment of peak purity was the introduction of hyphenated techniques. When selecting a method to perform a purity check, one has the choice between a global method which considers a whole peak cluster (from the start to the end of the peak), and evolutionary methods, which consider a window of the peak cluster, which is... 

Pharmaceutical Analysis Modern Methods (in two parts), edited by James W. Munson... 

G. Lunn, HPLC Methods for Pharmaceutical Analysis, Vol. 4, Wiley-Interscience Publication, John Wiley Sons, Inc., New York, 2000, pp. 1250-1256. 

Raggi et al. [21] described a spectrophotometric analysis method with ammonium tetrachloropalladate for penicillamine in pharmaceutical formulations. An aqueous solution of penicillamine (298 pg/mL) was treated with 1.5 mL of 20 mM (NH4)2PdCl4 in 1 M HC1. The mixture was diluted to 10 mL, and the absorbance measured at 403 nm after 20 min. The method has a recovery of 98.8%, and was used to determine penicillamine in aqueous extracts of capsules. 

R. E. Schirmer, in Modern Methods of Pharmaceutical Analysis, Volume HI, CRC Press, Boca Raton, Florida, 1982, pp. 157-169. 

Determination in Pharmaceutical Preparations The following tabulation of references high-lights those methods (see Section 5) useful in pharmaceutical analysis. 

Another potential benefit of UHPLC is its capability of solving the most challenging separation tasks in pharmaceutical analysis. Figure 9.4 shows a UPLC method developed to analyze pharmaceutical formulations used to treat the common cold. Cold products often contain multiple active ingredients to treat different symptoms and can contain decongestants, antihistamines, pain relievers, cough suppressants, expectorants, and numerous excipients of various polarities. The analysis of a total of 20 components was achieved within 10 min. 

Although considered a basic technique, ultraviolet-visible (UV-vis) is perhaps the most widely used spectrophotometric technique for the quantitative analysis of pure chemical substances such as APIs in pharmaceutical analysis. For pharmaceutical dosage forms that do not present significant matrix interference, quantitative UV-vis measurements may also be made directly.114,115 It is estimated that UV-vis-based methods account for 10% of pharmacopoeia assays of drug substances and formulated products.116... 

Applications of Karl Fischer Method for Determination of Water in Pharmaceutical Analysis... 

APPLICATIONS OF KARL FISCHER METHOD FOR DETERMINATION OF WATER IN PHARMACEUTICAL ANALYSIS... 

Schirmer, RE., Modem Methods of Pharmaceutical Analysis , 2nd ed., Boston, CRC Press, 1991. 

---