A study on the applicability of one-step vortex extraction and purification combined with gas chromatography-tandem mass spectrometry for analysis of four skin penetration enhancers in cosmetics.

Based on one-step vortex extraction and purification combined with gas chromatography-tandem mass spectrometry (GC-MS/MS), we established a simple, rapid, and efficient method for the simultaneous determination of four skin penetration enhancers in cosmetics, including isosorbide dimethyl ether, isopropyl myristate, N-butylsaccharin and Azone. The extraction procedure was performed in a centrifuge tube, allowing extraction and purification in a single step. The cosmetic sample was extracted by n-hexane-ethyl acetate (1:1, V/V), purified by silica gel and anhydrous magnesium sulfate as the solid phase purification agent, separated on a TG-5 ms column (30.0 m × 0.25 mm × 0.25 µ m), confirmed and detected by GC-MS/MS in the selected reaction monitoring (SRM) mode, and quantified by the internal standard method with Di-n­butyl phthalate-D4(DBP-D4) as the internal standard. The selections of a column, extraction solvent, and solid phase purification agent were optimized. Under the optimized conditions, the four skin penetration enhancers showed good linearities in the range of 0.02∼0.50 mg L - 1. The correlation coefficients (r) were 0.992 ∼ 0.997, exceeding the specifications requirements (r ≥ 0.990); The detection (LODs, S/N = 3) and quantification limits (LOQs, S/N = 10) of the method were 0.08 ∼ 0.12 mg kg-1 and 0.25 ∼ 0.40 mg kg-1, respectively. According to the cosmetic matrix in different formulation systems, the spiked recovery tests were carried out at three levels, i.e., low, medium, and high. The average recoveries of the analytes were 85.3% ∼ 95.6%, and the relative standard deviations (RSDs, n = 6) were 2.1% ∼ 7.8%. The established method was also employed to analyze cosmetics in the market. Azone, isosorbide dimethyl ether, and isopropyl myristate resulted as the most widely used skin penetration enhancers in cosmetics. The method established in this study has the advantages of operational simplicity, high sensitivity, good reproducibility, and low consumption of samples and solvents. Moreover, it can be used to determine skin penetration enhancers in cosmetics.

NMR method for accurate quantification of polysorbate 80 copolymer composition.

(13)C NMR spectroscopic integration employing short relaxation delays and a 30° pulse width was evaluated as a quantitative tool for analyzing the components of polysorbate 80. (13)C NMR analysis revealed that commercial polysorbate 80 formulations are a complex oligomeric mixture of sorbitan polyethoxylate esters and other intermediates, such as isosorbide polyethoxylate esters and poly(ethylene glycol) (PEG) esters. This novel approach facilitates the quantification of the component ratios. In this study, the ratios of the three major oligomers in polysorbate 80 were measured and the PEG series was found to be the major component of commercial polysorbate 80. The degree of polymerization of -CH2CH2O- groups and the ratio of free to bonded -CH2CH2O- end groups, which correlate with the hydrophilic/hydrophobic nature of the polymer, were analyzed, and were suggested to be key factors for assessing the likelihood of adverse biological reactions to polysorbate 80. The (13)C NMR data suggest that the feed ratio of raw materials and reaction conditions in the production of polysorbate 80 are not well controlled. Our results demonstrate that (13)C NMR is a universal, powerful tool for polysorbate analysis. Such analysis is crucial for the synthesis of a high-quality product, and is difficult to obtain by other methods.

Synthesis of 2-[(18)F]Fluoro-2-deoxyisosorbide 5-mononitrate and Assessment of Its in vivo Biodistribution as Determined by Dynamic Positron Emission Tomography (PET).

Herein we disclose the synthesis of 2-fluoro-2-deoxyisosorbide 5-mononitrate (2F-IS-5MN), a fluorinated analogue of the commonly prescribed vasodilator isosorbide 5-mononitrate (IS-5MN). X-ray structural data for IS-5MN and its C2-epimeric congener IM-5MN are presented together with structural data for 2F-IS-5MN. Radioisotope labeling of 2F-IS-5MN has, for the first time, allowed observation of the in vivo biodistribution of this organic nitrate by means of dynamic positron emission tomography (PET) in wild-type mice.

Quantification of myo-inositol, 1,5-anhydro- D-sorbitol, and D-chiro-inositol using high-performance liquid chromatography with electrochemical detection in very small volume clinical samples.

Inositol is a six-carbon sugar alcohol and is one of nine biologically significant isomers of hexahydroxycyclohexane. Myo-inositol is the primary biologically active form and is present in higher concentrations in the fetus and newborn than in adults. It is currently being examined for the prevention of retinopathy of prematurity in newborn preterm infants. A robust method for quantifying myo-inositol (MI), D-chiro-inositol (DCI) and 1,5-anhydro- D-sorbitol (ADS) in very small-volume (25 µL) urine, blood serum and/or plasma samples was developed. Using a multiple-column, multiple mobile phase liquid chromatographic system with electrochemical detection, the method was validated with respect to (a) selectivity, (b) accuracy/recovery, (c) precision/reproducibility, (d) sensitivity, (e) stability and (f) ruggedness. The standard curve was linear and ranged from 0.5 to 30 mg/L for each of the three analytes. Above-mentioned performance measures were within acceptable limits described in the Food and Drug Administration's Guidance for Industry: Bioanalytical Method Validation. The method was validated using blood serum and plasma collected using four common anticoagulants, and also by quantifying the accuracy and sensitivity of MI measured in simulated urine samples recovered from preterm infant diaper systems. The method performs satisfactorily measuring the three most common inositol isomers on 25 µL clinical samples of serum, plasma, milk, and/or urine. Similar performance is seen testing larger volume samples of infant formulas and infant formula ingredients. MI, ADS and DCI may be accurately tested in urine samples collected from five different preterm infant diapers if the urine volume is greater than 2-5 mL.

An outbreak of pyrimethamine toxicity in patients with ischaemic heart disease in Pakistan.

We investigated an outbreak of darkening of skin, bleeding from multiple sites, leucopenia and thrombocytopenia in ischaemic heart disease patients. Case patients were defined as patients who had received medicines from the pharmacy of Punjab Institute of Cardiology between 1 December 2011 and 12 January 2012 and who developed any one of the following: darkening of skin, bleeding from any site, thrombocytopenia and leucopenia. Clinical and drug-related data were abstracted. All 664 case patients had received iso-sorbide-mono-nitrate contaminated with about 50 mg of pyrimethamine, and 151 (23%) died. The median age of 117 patients admitted at Jinnah Hospital Lahore was 57 years (range, 37-100) and 92 (79%) were male. The median time from intake of medicine to presentation was 37 days (range 13-72). Symptoms and signs included bleeding (in 95% of the patients), skin hyperpigmentation (in 61%), diarrhoea (in 53%) and abdominal pain (in 48%). At presentation, the median white cell count was 2.3 × 10(9) /L (range, 0.1 × 10(9) -16.0 × 10(9) ), the median hemoglobin concentration was 109 g/L (range 58-169) and the median platelet count was 18 × 10(9) /L (range, 0 × 10(9) -318 × 10(9) ). Bone marrow examination revealed trileneage dysplasia and severe megaloblastosis. The predictors of mortality included presentation prior to 15 January 2012, age more than 57 years, hypotension and leukocyte count less than 1.5 × 10(9) /L. None of the patients who died received Calcium folinate because all deaths occurred prior to contaminant identification. We describe an outbreak of pyrimethamine toxicity in ischaemic heart disease patients receiving medicines from a single pharmacy due to accidental contamination of iso-sorbide mono-nitrate tablets at industrial level. Late recognition of illness resulted in high mortality.

Analysis and microbiological stability of an isosorbide 50% mixture.

Isosorbide mixture containing 50% w/v isosorbide and 5% w/v sorbitol is used in the treatment of hydrocephalus. The G.L.C. analysis of the mixture is described and its antimicrobial properties investigated. Results for the determination of lead in the mixture are given and the significance of the levels discussed with relevance to the treatment of infants.

Polarographic determination of isosorbide dinitrate.

Isosorbide dinitrate and two isomeric isosorbide mononitrates are shown to be polarographically reducible in aqueous sodium perchlorate or potassium chloride solution. The current, measured at -1.6 v, versus the saturated calomel electrode is proportional to the concentration of organic nitrate in the 10-100-mug/ml range. Inorganic nitrate produces no interference. However, the mononitrate isomers produce an additive response to isosorbide dinitrate and cannot be determined individually. The polarographic method is applicable to single-tablet assay for content uniformity determination, with precision and accuracy comparable to automated colorimetric analysis. Comparison is made between replicate analyses obtained polarographically and by IR and automated colorimetric analysis for six different commercially available formulations. The polarographic determination is sensitive, specific for nitrate esters, precise, requires little sample preparation, and utilizes relatively inexpensive apparatus.