Detection of undeclared erectile dysfunction drugs and analogues in dietary supplements by ion mobility spectrometry.

An ion mobility spectrometry (IMS) method was developed to screen for the presence of undeclared synthetic erectile dysfunction (ED) drugs or drug analogues in herbal dietary supplements claiming to enhance male sexual performance. Ion mobility spectra of authenticated reference materials including three FDA approved drugs (sildenafil citrate, tadalafil, vardenafil hydrochloride trihydrate) and five previously identified synthetic analogues (methisosildenafil, homosildenafil, piperidenafil, thiosildenafil, thiomethisosildenafil) were measured to determine their reduced ion mobilities (K(0)). All eight compounds exhibited reduced mobilities between 0.8257 and 1.2876 cm(2)/(Vs). Twenty-six herbal products were then screened for the presence of these compounds, and 15 of the 26 products tested positive for the presence of ED drug or drug analogue adulterants based on their reduced ion mobilities. IMS results were compared against the results obtained from an independent LC/MS reference method for the identical samples. Herbal dietary supplements containing adulterants were classified with 100% accuracy and most of the adulterants were correctly identified by a comparison of the K(0) of the adulterant to the K(0) of the authenticated reference material. The results demonstrate that IMS is a viable method for screening herbal dietary supplements for the presence of ED drug or drug analogue adulterants.

Screening of heparin API by near infrared reflectance and Raman spectroscopy.

Near infrared (NIR) reflectance and laser Raman spectra for a set of 69 heparin powder samples obtained from several foreign and domestic suppliers were measured. Both the NIR and Raman spectra of individual heparin API powder samples were correlated with sample compositions determined from response corrected relative peak areas of the capillary electropherograms of the samples using a partial least squares (PLS) regression model. Twenty-eight sample spectra were used to develop PLS models for the three major sample components; heparin, oversulfated chondroitin sulfate (OSCS) and glycosaminoglycans (GAGs). The PLS models were then used to successfully predict the compositions of 41 additional heparin samples. The success of these rapid, nondestructive technologies to identify contamination of heparin with OSCS demonstrates the potential of spectroscopy and chemometrics for screening of processed raw materials. These technologies are meant for screening purposes and not meant to replace either of the methods (capillary electrophoresis and NMR) currently required by USP and FDA.

Multivariate calibration of covalent aggregate fraction to the raman spectrum of regular human insulin.

Insulin aggregates were prepared by exposing samples of formulated regular human insulin to agitation at 60 degrees C. Aliquots were drawn from the samples periodically over a time range spanning 192 h, and their aggregate compositions were determined with size exclusion chromatography. The complete data set was composed of 39 separate aliquots. The Raman spectra of three separate 10 microL volumes from each aliquot were measured using the drop-coat deposition Raman (DCDR) method. The spectra were calibrated to aggregate composition by partial least squares regression (PLS), resulting in linear calibration (R(2) = 0.997) with a root mean squared error of calibration (RMSEC) of 1.3% and a root mean squared error of cross validation (RMSECV) of 5.1% in aggregate composition. Though the time required for aggregates to form under stressed conditions showed substantial sample-to-sample variation, the correlation between aggregate composition and Raman spectrum was remarkably consistent, indicating that Raman spectroscopy may be a viable screening method for aggregation of protein drugs.

Insulin temperature and stability under simulated transit conditions.

PURPOSE: The transit temperature profiles, mean kinetic temperatures (MKTs), and stability of insulin samples in both insulated and noninsulated containers exposed to summer and winter temperatures were evaluated. METHODS: Regular insulin, isophane insulin human (NPH) insulin, and 70% isophane-30% regular (70/30) insulin were packaged in the most commonly dispensed quantity of four vials in noninsulated mailers and insulated containers with frozen gel packs. After packaging, sealed containers and mailers were placed in an environmental chamber for 24-120 hours and exposed to summer and winter transit conditions. Temperatures inside the environmental chamber were recorded every 15 minutes and maintained within 3 degrees C of the specified transit temperature. After exposure to the transit conditions, insulin cartons were removed from their packaging, visually inspected for changes in physical appearance, and stored at 4 degrees C until analysis. The MKT of each package was calculated. High-performance liquid chromatography was performed to determine sample stability, and size-exclusion chromatography was conducted to detect aggregate products of insulin. RESULTS: Regardless of shipping conditions or packaging, all samples met the United States Pharmacopeia's ( USP's) specified limits and retained product stability. Visual inspection of the physical appearance of insulin samples before and after temperature exposure revealed results similar to those described in the product inserts. Microscopic analysis of the injectable suspensions confirmed similar crystal morphologies before and after temperature exposure. CONCLUSION: Regular, NPH, and 70/30 insulin maintained potency within USP limits when stored in programmable environmental chambers simulating summer and winter overnight or three- to five-day ground delivery conditions, regardless of packaging material.