Proceedings : A Forest Based Economy - Carrying A Tradition Into the Future

Proceedings : A Forest Based Economy - Carrying A Tradition Into the Future Blaine House Conference on Forestry (December 6-7, 1984) Department of Conservation, State House Station 22, Augusta, Maine 04333, August 1986. Contents: Table of Contents / Letter of Transmittal / The Forest 2020--Visions Of A Sustainable Forest / Forestry Resurvey: What Does It Say? How Can We Use It? / Can We Improve Maine\u27s Timber Supply? / Atmospheric Deposition And Forests Of The Northeast / A National Perspective: What Is Maine\u27s Competitive Niche? / The Future of Hardwood Markets / The Future of Softwood Markets / The State Of Our Forest / Trends In Maine\u27s Forest Transport System / Future Employment In The Maine Woods: Situation, Forces And Outlook / How Great Is The Threat From Canadian Labor? / The Threat From Imported Canadian Labor Is Alive and Well / Woods Labor Training Needs / A Condensed Report Of Wood Harvesting At The State\u27s VTI\u27s And What Is A Woodsman? / Safety and Workers Compensation / A Brief History Of Northern Woods Logging Association / A Maine Woodcutter Talks About Safety In the Woods / Maine\u27s Forest In The Global Context / Riding The Winds Of Change In Maine\u27s Foresthttps://digitalcommons.usm.maine.edu/me_collection/1172/thumbnail.jp

A tiered analytical approach for investigating poor quality emergency contraceptives.

Reproductive health has been deleteriously affected by poor quality medicines. Emergency contraceptive pills (ECPs) are an important birth control method that women can use after unprotected coitus for reducing the risk of pregnancy. In response to the detection of poor quality ECPs commercially available in the Peruvian market we developed a tiered multi-platform analytical strategy. In a survey to assess ECP medicine quality in Peru, 7 out of 25 different batches showed inadequate release of levonorgestrel by dissolution testing or improper amounts of active ingredient. One batch was found to contain a wrong active ingredient, with no detectable levonorgestrel. By combining ultrahigh performance liquid chromatography-ion mobility spectrometry-mass spectrometry (UHPLC-IMS-MS) and direct analysis in real time MS (DART-MS) the unknown compound was identified as the antibiotic sulfamethoxazole. Quantitation by UHPLC-triple quadrupole tandem MS (QqQ-MS/MS) indicated that the wrong ingredient was present in the ECP sample at levels which could have significant physiological effects. Further chemical characterization of the poor quality ECP samples included the identification of the excipients by 2D Diffusion-Ordered Nuclear Magnetic Resonance Spectroscopy (DOSY 1H NMR) indicating the presence of lactose and magnesium stearate

TLC analysis.

<p>Results for a levonorgestrel standard, sample 1 (positive control), and sample 2a observed under 254 nm light.</p

UHPLC-IMS-TOF-MS analysis.

<p>Extracted ion chromatogram (A) and extracted ion mobility chronogram (B) for a levonorgestrel standard with <i>m/z</i> 313.2168±0.005. Extracted ion chromatogram (C) and extracted ion mobility chronogram (D) for sulfamethoxazole standard with <i>m/z</i> 254.0599±0.005. Extracted ion chromatogram (E) and extracted ion mobility chronogram (F) for sulfamethoxazole in the poor quality contraceptive tablet with <i>m/z</i> 254.0599±0.005. Mass spectra for the target compounds are displayed as insets.</p

Precursor ion, fragmentor voltage, collision cell voltage, and product ions for sulfamethoxazole MRM analysis.

Q<p>Quantifying ion; ^C Confirming ion.</p

Summary of results for the ECP quality survey^a.

a<p>Product Labels – number indicates a different brand, where a subsequent letter indicates a different batch. Bold text indicates non-compliance. With the exception of 2a, all samples yielded compliant results for identification (TLC and confirmation of levonorgestrel through the HPLC evaluation for dextronorgestrel). No sample showed evidence of dextronorgestrel.</p>b<p>Dissolution presented with the stage required and average result.</p>c<p>Related Substances – the level of any single related substance (S) should be less than 1.0% and the total amount of related substances (T) should be less than 2.0%.</p>d<p>Assay and Content Uniformity results presented as the average results and the minimum / maximum result found.</p>e<p>Only Stage 1 was conducted because 3 tablets were found to be below 60%.</p>f<p>No active release was observed on the 6 tablets tested. Additional tablets were tested for longer periods of release (1 hour) and observed ∼2–5% release of active.</p>g<p>A single peak was observed in the chromatogram (other than for levonorgestrel) which made a large contribution to the level of observed impurities.</p>h<p>30 tablets tested.</p

HPLC-DAD analysis.

<p>HPLC chromatograms from assay / content uniformity analysis for a levonorgestrel standard, sample 1 (positive control), and sample 2a.</p

2D DOSY ¹H NMR analysis.

<p>Spectra (log D vs. chemical shift) for levonorgestrel-containing (A) and sample 2a (B) contraceptive tablets dissolved in CD₄O:D₂O (80∶20 v/v). Signals observed at 3.3 ppm and in the range 4.6–5 ppm are due to the deuterated solvent mixture.</p