Synthesis, high-performance liquid chromatography-nuclear magnetic resonance characterization and pharmacokinetics in mice of CD271 glucuronide.

Retinoic acid-glucuronides are known as retinoids with activity in acne therapy, limited placental transfer and reduced retinoid adverse effects. We synthesized the glucuronide of a novel retinoid, CD271 (adapalene), used for the treatment of moderate acne. The synthesis product ("CD271 glucuronide", CD271G) was purified by preparative HPLC. It undergoes in aqueous solution, like other glucuronides, rapid acyl-migration of the bound aglycone leading to position isomers. Thus characterization of purified CD271G could be only achieved by HPLC-NMR coupling. A subfraction ("CD271GB") consisting essentially of 2'- and 3'-CD271G was used for pharmacokinetic studies. After a single subcutaneous injection at a dosage of 30 mg/kg the substance showed considerable uptake and metabolism to CD271 indicating that CD271GB could serve as a prodrug for CD271.

Separation and identification of various carotenoids by C30 reversed-phase high-performance liquid chromatography coupled to UV and atmospheric pressure chemical ionization mass spectrometric detection.

In this paper the application of on-line HPLC-UV-APCI (atmospheric pressure chemical ionization) mass spectrometry (MS) coupling for the separation and determination of different carotenoids as well as cis/trans isomers of beta-carotene is reported. All HPLC separations were carried out under RP conditions on self-synthesized polymeric C30 phases. The analysis of a carotenoid mixture containing astaxanthin, canthaxanthin, zeaxanthin, echinenone and beta-carotene by HPLC-APCI-MS was achieved by scanning the mass range from m/z 200 to 700. For the characterization of a sample containing cis/trans isomers of beta-carotene as well as their oxidation products, a photodiode-array UV-visible absorbance detector was used in addition between the column and the mass spectrometer for structural elucidation of the geometrical isomers. The detection limit for beta-carotene in positive-ion APCI-MS was determined to be 1 pmol. In addition, an extract of non-polar substances in vegetable juice has been analyzed by HPLC-APCI-MS. The included carotenoids could be identified by their masses and their retention times.

Hyphenation of high performance liquid chromatography with nuclear magnetic resonance spectroscopy for the characterization of beta-carotene isomers employing a C30 stationary phase.

The hyphenation of HPLC together with NMR spectroscopy proves advantageous for the structure elucidation of oxidation- and UV-sensitive compounds such as beta-carotene isomers. In the closed-loop HPLC-NMR system, degradation or isomerization of separated compounds is largely hindered. With the help of 3-microm C30 stationary phases a better separation efficiency towards the different beta-carotene cis/trans isomers could be obtained in comparison to a 5-microm material, resulting in sharper peaks and a better resolution of all compounds. This effect greatly facilitated the structure determination of the isomers by HPLC-NMR coupling. Due to the introduction of a superior stationary phase, the structure of seven cis-isomers of beta-carotene could thereby be determined employing the stopped-flow HPLC-1H-NMR mode.

Public health nursing practice guidelines: an evaluation of dissemination and use.

Public health nursing needs to build a practice on research-based knowledge. Public health guidelines are one strategy to achieve this goal. Using research-based knowledge, the Minnesota Practice Enhancement Project (MPEP) developed positive parenting and family violence prevention guidelines for public health nurses (PHNs). The purpose of this study was to evaluate the dissemination and use of the MPEP guidelines using a survey of PHNs and telephone interviews of public health nursing directors. Results indicated that respondents viewed the guidelines as important, but identified numerous barriers to integrating the guidelines into their practice. Major barriers included lack of time in their work day, complex guideline structure, and competing agency demands and priorities. Findings were consistent with Roger's Diffusion of Innovations theory, which describes factors associated with the adoption of a new idea or practice. Recommendations for effective dissemination include administrative support and structure to increase PHN intentional use of practice guidelines, a simplified guideline format, and mentorship in guideline use.

Separation and Identification of Tocotrienol Isomers by HPLC-MS and HPLC-NMR Coupling.

A crude palm-oil extract rich in vitamin E homologues was investigated by HPLC-MS and HPLC-NMR coupling. For mass spectrometry a newly introduced ionization technique called Coordination Ion Spray (CIS) was used. Through the addition of silver ions to the HPLC eluent, the ionization process of nonpolar substances is facilitated. Chromatography and all coupling experiments were conducted on a C(30) column which exhibited an extraordinary shape selectivity and overwhelming sample-loading capability. Experiments were performed with pure methanol as an eluent which proved to be ideal for NMR spectroscopy as well as mass spectrometry. All necessary information for unambiguous structural assignment was collected within 45 min of the LC-NMR experiment and 15 min of the LC-MS experiment. Six compounds were identified, i.e., α-, ß-, γ-, and δ-tocotrienol, α-tocoenol, and α-tocopherol.

Silver-plated vitamins: a method of detecting tocopherols and carotenoids in LC/ESI-MS coupling.

In LC/MS, nonpolar substances in the majority of cases cannot be ionized by standard electrospray ionization (ESI) because they obviously lack a site for protonation or deprotonation. The ionization of carotenoids and tocopherols can be greatly enhanced by the addition of silver ions. The Ag(+)-carotenoid and Ag(+)-tocopherol adducts thus formed render these substances amenable to MS. alpha-, beta-, gamma-, and delta-tocopherol, alpha-tocopherol acetate, and the various isomers of lycopene and beta-carotene were separated by C30 RP-HPLC and could be identified by online ESI-MS. A mixture of six different carotenoids was analyzed by scanning the mass range from m/z 500 to 800. The mass spectra of the peaks revealed that all carotenoids and most tocopherols were partially oxidized to radical cations. The detection limit for canthaxanthin was approximately 500 fmol while that of beta-carotene was below 300 fmol. An increase in sensitivity in the MRM mode can be attained by monitoring ions formed by loss of elemental silver from the adducts in the CID cell. Dichloromethane extracts of tomato, carrot, and vegetable juices, a vitamin drink, and a commercial infant food product were analyzed by LC/MS. After postcolumn argentation, from the mass-selective extracts of the TIC, the carotenoids and tocopherols present could be identified by their masses and their retention times. For all studies, a silver perchlorate solution with an overall concentration of 50 micrograms/mL was used.

Population-based public health nursing interventions: a model from practice.

In a changing and complex health care system, public health nurses face challenges to explain their work and contributions to health outcomes. In response to this need, the Minnesota Department of Health, Section of Public Health Nursing, initiated a process to describe public health nursing interventions. The Public Health Nursing Interventions (PHI) Model was developed through a collaborative process by public health nurses at the state and local levels. The purpose of the model was to define more clearly the practice of public health nursing and to describe better the work of public health nurses at the community and systems levels. The PHI model identifies 17 interventions and provides practice examples at the systems, community and individual/family levels. The model defines a broader view of the mission and scope of public health nursing. Practice examples are given for agency staff, administrators, educators, and policy makers.

Shape selectivity of C30 phases for RP-HPLC separation of tocopherol isomers and correlation with MAS NMR data from suspended stationary phases.

Vitamin E (tocopherol) acts in various organisms as the main free radical scavenger. This capacity, which is enhanced by the synergetic effect of vitamin C and carotenes, points to a possible application as anti-tumor agent in chemotherapy. There are several isomeric forms, namely alpha-, beta-, gamma-, and delta-tocopherol, having different antioxidative abilities, with alpha-tocopherol being the most biologically active. Using methanol as eluent and a C30 stationary phase, we achieved complete separation of alpha-, beta-, gamma-, and delta-tocopherol and alpha-tocopherol acetate by RP-HPLC within 14 min. Detection was performed by UV and 1H NMR spectroscopy. The advantage of NMR is the possibility of structural identification of chromatographic peaks. Also, coeluting peaks are easily recognized. The enhanced shape recognition of the C30 phase has been attributed to the high order of the alkyl chains of the stationary phase. This has, so far, been proven by solid-state NMR spectroscopy. We now introduce the technique of 13C MAS NMR spectroscopy of suspended stationary phases. The resulting NMR spectra reveal that, in the presence of weak eluents, like methanol, the overall high order of the C30 chains is slightly altered, whereas in stronger eluents, like MTBE, the alkyl chains possess a higher mobility.

Capillary HPLC-NMR Coupling: High-Resolution (1)H NMR Spectroscopy in the Nanoliter Scale.

Coupling HPLC and NMR is one of the most powerful techniques for simultaneous separation and structural elucidation of unknown compounds in mixtures. To date, however, minimizing the detection volume, as is required when coupling NMR with miniaturized separation techniques, has been accompanied by a dramatic loss in resolution of the NMR spectra. Here, we report on the coupling of gradient capillary HPLC with on-column, high-resolution NMR detection. On-line stopped-flow and static (1)H NMR spectra were acquired with capillary columns of 75-315 µm i.d. With detection over a length of 1.2 cm, cell volumes cover a range of 50-900 nL. An on-line-detected NMR separation of dansylated amino acids was carried out in a 315 µm i.d. fused silica capillary packed to a length of 12 cm with C(18) stationary phase. The low solvent consumption makes the use of fully deuterated solvents economically feasible. NMR spectra with resolution on the order of 3 Hz were obtained using a 50 nL detection cell to measure 1.1 nmol of dansylated γ-aminobutyric acid under static conditions in a 75 µm i.d. capillary.

Managing uncompensated home care.

The purpose of this study was to determine the strategies used by managers of public health nursing and visiting nurse associations to cope with increased demand for uncompensated home care. A questionnaire was mailed to all public health nursing and visiting nurse associations in the upper midwest. Of the 161 agencies reporting their experience with uncompensated care demand, 129 experienced an increased demand for uncompensated care. Public health nursing and small agencies were more likely to experience increased demand for uncompensated care. Use of cost reduction, revenue enhancement, and quality assurance strategies varied by demand for uncompensated care status as well as by agency size and type. Managers of large and medium agencies and visiting nurses associations were more likely to use the identified strategies. Six strategies were used by more than 50% of the responding agencies.