Apollo Next Generation Sample Analysis (ANGSA): an Apollo Participating Scientist Program to Prepare the Lunar Sample Community for Artemis.

As a first step in preparing for the return of samples from the Moon by the Artemis Program, NASA initiated the Apollo Next Generation Sample Analysis Program (ANGSA). ANGSA was designed to function as a low-cost sample return mission and involved the curation and analysis of samples previously returned by the Apollo 17 mission that remained unopened or stored under unique conditions for 50 years. These samples include the lower portion of a double drive tube previously sealed on the lunar surface, the upper portion of that drive tube that had remained unopened, and a variety of Apollo 17 samples that had remained stored at -27 °C for approximately 50 years. ANGSA constitutes the first preliminary examination phase of a lunar "sample return mission" in over 50 years. It also mimics that same phase of an Artemis surface exploration mission, its design included placing samples within the context of local and regional geology through new orbital observations collected since Apollo and additional new "boots-on-the-ground" observations, data synthesis, and interpretations provided by Apollo 17 astronaut Harrison Schmitt. ANGSA used new curation techniques to prepare, document, and allocate these new lunar samples, developed new tools to open and extract gases from their containers, and applied new analytical instrumentation previously unavailable during the Apollo Program to reveal new information about these samples. Most of the 90 scientists, engineers, and curators involved in this mission were not alive during the Apollo Program, and it had been 30 years since the last Apollo core sample was processed in the Apollo curation facility at NASA JSC. There are many firsts associated with ANGSA that have direct relevance to Artemis. ANGSA is the first to open a core sample previously sealed on the surface of the Moon, the first to extract and analyze lunar gases collected in situ, the first to examine a core that penetrated a lunar landslide deposit, and the first to process pristine Apollo samples in a glovebox at -20 °C. All the ANGSA activities have helped to prepare the Artemis generation for what is to come. The timing of this program, the composition of the team, and the preservation of unopened Apollo samples facilitated this generational handoff from Apollo to Artemis that sets up Artemis and the lunar sample science community for additional successes.

Hazards associated with the boat building industry in New Zealand: an OSH audit.

AIM: To randomly audit the boat building industry in New Zealand to assess the occupational health status and level of knowledge of employees. METHODS: A survey was conducted using a nurse and inspector administered questionnaire. 151 workers from 120 randomly selected firms participated in the survey. RESULTS: 31.5% respondents thought they had had some sort of work related health problem since working in that job. 22% reported wheezing during the last twelve months. 14-16% met criteria for occupational causation, and 4% met a measure of severe wheezing related to work. 25.6% of workers had dermatitis. Only a quarter of these met criteria for occupational causation. No respondents reported symptoms suggestive of chronic solvent neurotoxicity. Solvents and epoxy resins comprised the majority of chemicals with which there was contact. Observation suggested little use of Material Safety Data Sheets as a source of knowledge about toxicity of the chemicals used. Although 94.3% reported wearing gloves, this did not correlate with numbers reporting dermatitis suggesting non-compliance or glove failure. CONCLUSION: New Zealand boat builders and their employees remain at risk for occupational health problems by virtue of their employment.

No association found between polymorphisms in genes encoding mGluR7 and mGluR8 and idiopathic generalised epilepsy in a case control study.

The genes of two group III metabotropic glutamate receptors, mGluR7 and 8, are candidate susceptibility genes for epilepsy. The Tyr433Phe polymorphism of mGluR7 and a novel polymorphism in the mGluR8 gene located 29 bp after the termination codon (2756C/T) were investigated in case control association studies performed on DNA from more than 100 patients with idiopathic generalised epilepsy (IGE). No significant association was found with IGE for either polymorphism.

Effect of dominant follicle persistence on follicular fluid oestradiol and inhibin and on oocyte maturation in heifers.

The aim of the present study was to characterize in detail the cytoplasmic and nuclear morphology of cattle oocytes recovered from follicles that are dominant for more than 9 days (with low fertility after ovulation), and to relate morphological changes to intrafollicular markers of follicle health. Beef heifers received prostaglandin F2 alpha and a synthetic progestagen (3 mg Norgestomet) for 2 or 10 days on the first day of dominance of the second dominant follicle (DF2) of the oestrous cycle, to give a 4 day (n = 19; N2) or 12 day (n = 21; N10) duration of dominance of the dominant follicle at ovariectomy 18 h after implant removal and before the predicted gonadotrophin surge. Ultrasound scanning determined emergence of a new wave of follicles in five N10 heifers the day before (n = 1) or day of ovariectomy (n = 4) (N10-NonDom). Dominant follicles from the remaining N10 heifers (N10-Dom) were larger (P < 0.05) on the day of ovariectomy (17.8 +/- 0.6 mm) than those from N2 heifers (13.6 +/- 0.4 mm). The oestradiol:progesterone ratio of follicular fluid from N10-Dom heifers was reduced (21.7 +/- 3.1 versus 34.1 +/- 4.4; P < 0.05), while inhibin A (as measured by immunoradiometric assay) was increased (12.7 +/- 1.0 versus 9.0 +/- 0.7 micrograms ml-1; P < 0.05) compared with N2 heifers. Eleven of twelve N2 oocytes demonstrated nuclear activation without germinal vesicle breakdown, while seven of eight N10-Dom oocytes had undergone germinal vesicle breakdown and had progressed to metaphase I (6/8) or II (1/8). In contrast to N2 oocytes, N10-Dom oocytes showed a larger perivitelline space containing more cumulus cell process endings, vacuoles, irregular vesicles, and more mitochrondia and lipid droplets throughout the ooplasm, yet the degree of cumulus cell expansion and atresia was similar. Thus, final oocyte maturation leading to metaphase I is initiated in most dominant follicles with a dominance period of > 9 days before the gonadotrophin surge and is associated with a reduction in dominant follicle health. However, ovulatory ability is maintained and will lead to the ovulation of aged oocytes, markedly reducing subsequent pregnancy rates.

High-pressure liquid chromatographic methods for ciprofloxacin hydrochloride and related compounds in raw materials.

High-pressure liquid chromatographic (HPLC) methods were developed for the analysis of ciprofloxacin hydrochloride raw materials. Method A is for drug content and the determination of related compounds eluting before the drug, including the ethylenediamine analog of ciprofloxacin. Method B may be used for the determination of fluoroquinolonic acid and other related compounds eluting after the drug. Both methods require a 5 microns Inertsil ODS2 column (150 x 4.6 mm), a mobile phase containing tetrahydrofuran, acetonitrile and buffer (0.005 M 1-hexane-sulphonic acid sodium adjusted to pH 3.0 with 0.1 M phosphoric acid); 10:5:85 (v/v/v) for method A and 25:15:60 (v/v/v) for method B, and a flow rate of 1 ml min-1. Detection for method A is at 254 nm; a programmable variable wavelength detector is required for method B: 254 nm for 12 min, then 220 nm for 23 min. The limit of quantitation of the related compounds was 0.05% or less. The precision of the assay method was lower than 1.0%. Drug content in four raw material samples ranged from 98.7% to 101.6% calculated with reference to the anhydrous substance. The water content in these samples ranged from 5.9% to 7.8%. Total impurity levels were 1.0% or lower. Levels of ethylenediamine analog and fluoroquinolonic acid were below 0.4%. A second analyst, using a different HPLC system and a column from a different supplier, repeated the analysis of two raw materials samples and obtained similar results.

Nadolol: high-pressure liquid chromatographic methods for assay, racemate composition and related compounds.

High-pressure liquid chromatographic (HPLC) methods have been developed for the determination of drug content, racemate A and related compounds in nadolol raw materials. The method for drug content and related substances resolved seven related compounds and several unknown impurities from the drug. The minimum quantifiable levels were 0.05% or less for four of the seven related compounds and 0.3% or less for the remainder. Total impurities in eight raw material samples ranged from 0.06 to 0.96% and assay levels ranged from 98.7 to 101.0%. The method was adapted for the determination of nadolol racemate A by a change in mobile phase composition. One raw material sample contained less than 40% of racemate A. Two samples which had a granular appearance were variable in racemate A content. The methods were adapted for the determination of drug and racemate A in nadolol tablets. Drug content in three tablet samples was between 96.2 and 98.4% and racemate A content was about 52%.

Does the acetyl group of aspirin contribute to the antiinflammatory efficacy of salicylic acid in the treatment of rheumatoid arthritis?

In a multicenter, double-blind, parallel-group study, 233 patients with classical or definite RA who demonstrated disease flare during a prestudy washout period were randomized to 12 weeks of treatment with either the nonacetylated salicylate, salsalate (salicylsalicylic acid), or aspirin. Of the 150 patients who completed the study, 83 received salsalate and 67 were treated with aspirin. Doses of the two drugs were calculated to provide equal amounts of bioavailable salicylic acid. The efficacy of salsalate and aspirin, as measured by all the usual variables, was equivalent but aspirin-treated patients had a higher incidence of severe gastrointestinal problems. Thus, this study demonstrated that the acetyl group of aspirin does not enhance the anti-inflammatory efficacy of salicylic acid in RA.

Liquid chromatographic methods for vitamins A and D in multivitamin-mineral formulations.

Liquid chromatographic screening procedures have been developed for the estimation of vitamins A and D in multivitamin-mineral tablet, capsule, gelatin capsule, and syrup formulations. The procedure can be used for measuring vitamin A present as either retinyl acetate or retinyl palmitate, and also for measuring the contribution to total vitamin A activity from 13-cis retinyl esters. The retinyl esters and their isomers are resolved from each other and their oxidation products. Ergocalciferol and cholecalciferol are not resolved from each other but they are resolved from other vitamin D isomers and from vitamins A, E, and K and their degradation products. Both assays use a 3 microns amino column, with a mobile phase of hexane for vitamin A and 1% isopropanol in hexane for vitamin D. The precision of replicate injections for vitamins A and D is better than 1% and the recovery from spiked syrups is better than 98%. The coefficient of variation for both assay methods is about 5%. Twenty formulations were analyzed for vitamin A and 24 were analyzed for vitamin D.

Liquid chromatographic methods for assay of carbamazepine, 10,11-dihydrocarbamazepine, and related compounds in carbamazepine drug substance and tablets.

Liquid chromatographic (LC) methods have been developed for the determination of carbamazepine, the impurity 10,11-dihydrocarbamazepine, and related compounds in carbamazepine drug substance and tablets. The LC methods specify a 5 micron diol column and a mobile phase of acetonitrile-methanol-0.05% aqueous acetic acid (5 + 5 + 90). Iminodibenzyl and iminostilbene, starting materials for some routes of synthesis, elute late in the LC system; therefore, a thin-layer chromatographic method for their detection at the 0.05% level has been developed. Eight tablet and 13 raw material samples from several sources were examined. The impurities most frequently found were 10, 11-dihydrocarbamazepine and a compound identified as 10-bromocarbamazepine at levels up to 1.3 and 0.5%, respectively; minimum detectable amounts were about 0.01 and 0.03%, respectively.

Determination of hydrazine in pharmaceuticals IV: Hydrazine and benzylhydrazine in isocarboxazid.

A GC procedure for the simultaneous determination of hydrazine and benzylhydrazine in isocarboxazid raw material and tablet formulations has been developed. The method is based on the reaction of benzoyltrifluoroacetone with hydrazine and benzylhydrazine to form the corresponding pyrazole derivatives. The minimum detectable amounts of hydrazine and benzylhydrazine in isocarboxazid are 0.002 and 0.02%, respectively.

Determination of azobenzene and hydrazobenzene in phenylbutazone and sulfinpyrazone products by high-performance liquid chromatography.

A high-performance liquid chromatographic method has been developed for the simultaneous determination of azobenzene and hydrazobenzene in phenylbutazone and sulfinpyrazone raw materials and formulations. The drug raw material or formulation is shaken with 1N NaOH and n-hexane and centrifuged. The n-hexane layer is injected into a chromatograph equipped with a 10-micron cyano-amino bonded phase column. Azobenzene and hydrazobenzene are detected at 313 and 254 nm, respectively; the sensitivities are approximately 1 and 2 ppm, respectively, in the raw materials and formulations.

Hydrazine levels in formulations of hydralazine, isoniazid, and phenelzine over a 2-year period.

Hydrazine levels in formulations of hydralazine, isoniazid, and phenelzine have been measured over a 2-year period under ambient conditions and under temperature and humidity stress. Hydralazine tablets are stable under ambient conditions, but the hydrazine level in an injectable formulation increased from 4.5 to 10 micrograms/ml over a 23-month period. Isoniazid tablets are also stable, but hydrazine levels in an elixir and a pyridoxine combination product doubled to 44 micrograms/ml and 19 micrograms/tablet, respectively. Levels in phenelzine tablets appeared to remain constant at approximately 60 micrograms/tablet, with considerable tablet-to-tablet variation.

Impurities in drugs IV: Indomethacin.

One lot of indomethacin raw material, five lots of capsule preparations, and three lots of supporitory formulations were screened for impurities by TLC. Only the suppository products exhibited impurities above trace levels. The two main impurities were present at levels estimated at approximately 0.5 and 2%. After isolation from preparative TLC plates, they were identified by NMR, IR, and mass spectroscopy as the alpha-substituted monoglyceryl esters of 4-chlorobenzoic acid and indomethacin, respectively.

Impurities in drugs III: Trihexyphenidyl.

Two lots of trihexyphenidyl hydrochloride raw material, one lot of elixir, and 10 lots of tablets were examined for impurities by TLC. Impurities found were 1-phenyl-2-propenone, 3-piperidinopropiophenone, and 3-aminopropiophenone. Not all impurities were present in all lots, and none exceeded 1.9% of the label drug claim. Impurities were identified by mass spectrometry and by comparison of TLC Rf values and GLC retention times to those of synthesized specimens of the impurities.

Impurities in drugs I: Imipramine, desipramine, and their formulations.

Nineteen lots of imipramine tablets and four lots of desipramine tablets were examined for impurities by TLC. Iminodibenzyl, desipramine, and 10,11-dihydro-5-[3-(methylamino-3'-dimethylaminopropyl)propyl]-5H-dibenz[b,f]azepine dihydrobromide (I) were found in some imipramine tablets, and iminodibenzyl and imipramine were found in some desipramine tablets, all at levels of less than 0.3% of label claim of the drug. Except for I, the identity of the impurities was established by comparison with known standards; I was synthesized and its composition was established by elemental analysis. All impurities, including I, were characterized by TLC, GLC, and mass spectrometry.

GLC assay of conjugated estrogen formulations.

A procedure is described for the enzyme hydrolysis and GLC assay of conjugated estrogens in commercial formulations. Resolution of up to nine of the components is achieved on a methyl phenyl cyanopropyl silicone-coated column using a dual-derivatization and dual-injection technique. Replicate results from analyses of a commercial tablet formulation yielded coefficients of variation between 1.0 and 17.2%, depending mainly on the quantity present; a coefficient of variation of 0.4% was obtained for the assay for total conjugated estrogens. Similar results were obtained with other commercial formulations.