Albuterol

Sample preparation 2 mL Whole blood or plasma + 2 mL buffer -I- 5 mL chloroform isopropanol n-heptane 60 14 26, shake gently horizontally for 10 min, centrifuge at 2800 g for 10 min. Remove the lower organic layer and evaporate it to dryness under vacuum at 45°, reconstitute the residue in 100 ixL mobile phase, centrifuge at 2800 g for 5 min, inject a 50 xL ahquot of the supernatant. (Buffer was saturated ammonium chloride solution 25% diluted with water, adjusted to pH 9.5 with 25% ammonia solution.) 

Mobile phase MeOH THF buffer 65 5 30 (Buffer was 0.68 g/L (10 mM (sic)) KH2PO4 adjusted to pH 2.6 with concentrated orthophosphoric acid.) (At the end of each session wash the column with water for 1 h and MeOH for 1 h, re-equilibrate for 30 min.) 

Interfering aspirin, atenolol, chlormezanone, codeine, metformin, morphine, phenobarbi-tal, phenol, ranitidine, ritodrine, sultopride, terbutaline, tiapride, toloxatone 

Tracqui, A. Kintz, R Mangin, P. Systematic toxicological analysis using HPLC/DAD. J.Forensic Sci., 1995, 40, 254-262 

Mobile phase MeOH buffer 25 75 (Buffer was 70 mM NaH2P04 + 1 mM chloride + 2 mM 1-heptanesulfonic acid, pH 6.8.) 

A mixture of 6.65 g of 3-chloro-6-nitroacetanilide, 3.2 ml of propylmercaptan, 5.6 g of 50% sodium hydroxide and 100 mi of water Is heated at reflux overnight. The cooled mixture is filtered to give the desired 2-nitro-5-propyithioaniline, MP 69.5°-71.5°C after recrystailiza-tion from ethanoi then hexane-ether. NMR (CDCi3) 40%. 

Theaniiine (2.5 g) is hydrogenated with 1.9 mi of concentrated hydrochloric acid, 100 mi ethanoi and 5% paiiadium-on-charcoal to give 4-propyithio-o-phenyiene diamine hydrochloride. 

A mixture of 25 ml of 50% sodium hydroxide in 5 ml of water is added to a mixture of 15 g of cyanamide, 2.2 g of methylchloroformate, 3.5 ml of water and 3 ml of acetone over 45 minutes below 10°C, pH raised to 6.5. A moiar equivaient soiution of the diamine in 100 ml of ethanol isadded. The mixture is heated until the easily volatile solventsare expelled, to about 85°C, then maintained at this temperature with some water added for one-half hour. The product, methyl 5-propylthio-2-benzimidazolecarbamate, is separated, washed to give a colorless crystalline solid, MP 208°-210°C. 

Gyurik, R,J. and Theodorides, V J. U.S. Patent 3,915,986 October 28,1975 assigned to Smith Kline Corp. 

Chemical Name a -[[(1,1-Dlmethylethyl)amino]methyl]-4-hydroxy-1,3-benzenedimethanol Common Name Salbutamol a -tert-butylaminomethyl-4-hydroxy-m-xylene-ai,Q 3.diol Structural Formula ciIjOH 

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Most of the drugs such as epinephrine and albuterol used to treat asthma attacks are bronchodilators—substances that expand the bronchial passages Newer drugs are designed to either inhibit the enzyme 5 lipoxygenase which acts on arachidomc acid m the first stage of leukotriene biosynthesis or to block leukotriene receptors... 

Clenbuterol [37148-27-9] C 2H gCl2N20, (6) (54), a nonphenolic analogue of terbutaline, is not susceptible to COMT or to conjugation. It has a long plasma half-life (20 h), but does not seem to differ ia pharmacological half-life from albuterol (55). 

The action of epinephrine and related agents forms the basis of therapeutic control of smooth muscle contraction. Breathing disorders, including asthma and various allergies, can result from excessive contraction of bronchial smooth muscle tissue. Treatment with epinephrine, whether by tablets or aerosol inhalation, inhibits MLCK and relaxes bronchial muscle tissue. More specific bronchodilators, such as albuterol (see figure), act more selec-... 

Fig. 2-7. Chromatograms of albuterol in the new polar organie phase on vaneomyein (A), teieoplanin (B), ristoeetin A (C), vaneomyein + teieoplanin (D), ristoeetin A + vaneomyein (E), and ristoeetin A + vaneomyein + teieoplanin (F). All eolumns were 100 x 4.6 mm. The numbers by the peaks refer to the retention time in minutes. The mobile phase was methanol with 0.02 % glaeial aeetie aeid and 0.01 % triethylamine (v/v). The flow rate was 2.0 mL min at ambient temperature (23 °C).

Although very efficient, the broad application of the direct preparation is restricted due to the limited number of pure starting enantiomers. The design of a multistep process that includes asymmetric synthesis is cumbersome and the development costs may be quite high. This approach is likely best suited for the multi-ton scale production of commodity enantiomers such as the drugs ibuprofen, naproxen, atenolol, and albuterol. However, even the best asymmetric syntheses do not lead to products in an enantiomerically pure state (100 % enantiomeric excess). Typically, the product is enriched to a certain degree with one enantiomer. Therefore, an additional purification step may be needed to achieve the required enantiopurity. 

Examples of sympathomimetic bronchodilators include albuterol (Ventolin), epinephrine (Adrenalin), salme-terol (Serevent), and terbutaline (Brethine). Many of the sympathomimetics used as bronchodilators have die subclassification of beta-2 ((32) receptor agonists (eg, albuterol, salmeterol, and terbutaline). Additional information concerning the various sympathomimetic dragp is given in the Summary Drug Table Bronchodilators. 

An inhaled sympathomimetic, such as albuterol, may be prescribed initially. Salmeterol, a long-acting (5-agonist, is contraindicated because of its slowed onset of action. During an acute bronchospasm, the nurse checks the blood pressure pulse, respiratory rate, and response to the drug every 15 to 35 minutes until the patient s condition stabilizes and respiratory distress is relieved. 

If bronchospasm present, use albuterol nebulization 2.5-5 mg every 20 min for 3 doses or racemic epinephrine nebulization 0.5 mL every 3 1 h as needed... 

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