Qualitative and quantitative analyses of pharmaceutical products using near-IR spectrometry have become popular. The flexibility of near-IR spectrometry in adapting to the use of powders, solutions, intact tablets(1), capsules, packaging materials, etc., has played a large role in its popularity. Near-IR spectrometry is quick, simple, inexpensive and nondestructive, in contrast to many other analytical techniques. A finished product can be analyzed by near-IR spectrometry and sold or consumed after the analysis.
Acoustic-resonance spectrometry (ARS) enjoys sample preparation advantages similar to those of near-IR spectrometry. In ARS, an ultrasonic wave with swept frequency is launched into a tablet from one or more directions, and the absorbance and phase shift of this wave in the sample are monitored. Like near-IR spectrometry, the new ARS technique has also been used to examine finished pharmaceutical tablets and to estimate tablet dissolution rate(2).
Tablet recall. A batch of 17-alpha-methyltestosterone tablets, an oral prescription drug used for replacement therapy in males, was recalled from the market by the FDA(3). The 10 mg dose in 100 tablet bottles was available under the following labels: Richlyn Laboratories, Inc.; Schein Pharmaceutical, Inc.; Goldline Laboratories; Rugby Laboratories, Inc.; Major Pharmaceutical Corporation; and United Research Laboratories, Inc. The reason given for the recall was that a bottle of methyltestosterone tablets was found to contain a foreign tablet identified as Richlyn meclizine (25 mg).
17-alpha-methyltestosterone, a steroid, has long been used as an androgenic agent. Meclizine, on the other hand, is a piperazine derivative used mainly as an anti-emetic . Methyltestosterone and meclizine tablets have completely different therapeutic applications, and confusion of one with the other could be disastrous to an aircraft pilot, for example. In this case as well as many others, it is imperative to find a simple and effective method of distinguishing the drugs in their tablet form before labeling.
The USP describes a destructive method of identification of 17-alpha-methyltestosterone and meclizine tablets(4). Identification of methyltestosterone requires that: a. the infrared absorption spectrum of a potassium bromide dispersion of methyltestosterone, previously dried, exhibits maxima only at the same wavelengths as that of a similar preparation of USP methyltestosterone RS. b. the ultraviolet absorption spectrum of a 1 in 100,000 solution of methyltestosterone in alcohol exhibits maxima and minima at the same wavelengths as that of a similar preparation of USP methyltestosterone RS, concomitantly measured.
Identification of meclizine requires that a. the infrared absorption spectrum of a potassium bromide dispersion of meclizine hydrochloride exhibit maxima only at the same wavelengths as that of similar preparation of USP meclizine hydrochloride RS. b. the ultraviolet absorption spectrum of a 1 in 100,000 solution of meclizine hydrochloride in dilute hydrochloric acid (1 in 100) exhibit maxima and minima at the same wavelengths as that of a similar solution of USP meclizine hydrochloride RS, concomitantly measured, and the respective absorptivities, calculated on an anhydrous basis at the wavelength of maximum absorbance near 232 nm, not differ by more than 3.0%.
The goals of this research are
1. to test the hypothesis that NIR/ARS identifies meclizine and methyltestosterone tablets more accurately than near-IR spectrometry alone, and
2. to test the hypothesis that bootstrapping principal components provides important information on the reliability of wavelengths in principal-component regression with spectra.