Lab

Target based assay

must identify a crucial biochemical process or pathway where modulation alleviates disease symptoms

Cell based assay

effect on the cell being studies may lead to improvement of disease symptoms

Stationary phase

silica gel on an aluminum foil backing

Mobile phase

mixture of hexanes/ethyl acetate

Reversible inhibitors

bind to the enzyme via noncovalent interactions

Irreversible inhibition

covalent bond forms between the inhibitor and the target enzyme

Competitive inhibitor

binds the enzyme at the active site and reduces the fraction of enzyme bound to the substrate

Non Competitive inhibitor

binds the enzyme at a different site than the substrate and decreases the activity of the enzyme

Hydrophilic

molecules are relatively polar

• are insoluble in nonpolar solvents like hexane and toluene

  • often contain amines, carboxylic acids, or hydroxyls as functional group

Lipophilic

molecules are nonpolar

• display low water solubility

  • most atoms are carbon and hydrogen

P

= [compound]oct/[compound]aq

Log P

= log ([compound]oct/[compound]aq)

If P>1

the molecule is more soluble in 1-octanol and Log P is positive

Solubility

describes how much of a compound can dissolve in a solvent (how much drug can dissolve in a aqueous medium)

Permeability

describes how quickly a compound can pass through a membrane

Strong base

will cause complete dissociation of a weak acid in aqueous solution permitting the determination of the pKa

Sulfonamides

inhibit dihydropteroate synthase (DHPS) in the folate synthesis pathway

Tetracycline

inhibits bacterial protein synthesis

Penicillin G

interferes with bacterial cell wall synthesis

Z’ score

uses positive and negative control averages and standard deviations to assess assay quality

UV/Visible spectroscopy

involves the absorption of UV/Visible light by a molecule causing the promotion of an electron from a ground electronic state to an excited electronic state

Short wavelength cutoff

is due to the absorption by the lens of the eye

Long wavelength cutoff

is due to the decrease in sensitivity of the photoreceptors in the retina for longer wavelengths

Bathochromic shift

salicylic acid iron complex has a maximum absorption wavelength that is longer than salicylic acid

A= e c l

The Beer Lambert Law relates absorption to the concentration of molecules

• is impacted by a constant and the path length

• is not impacted by the intensity of the incident light

Cation exchanger

bound anions- anions elute first then cations

Anion exchanger

bound cations- cations elute first then anions

K=0

molecules >100,000 will be totally excluded (eluted first, with no resolution)

0<K<1

10,000<molecules<100,000 will be eluted based on size (larger molecules first)

K=1

molecules<10,000 will be totally included (eluted last, with no resolution)

Partition coeffieient

drug between an organic phase and water is used as an indicator of the drug’s ability across biological membranes

Small intestine

the main site of drug absorption in part due to high surface area of approximately 400 m2

The Overton Rule

the relative lipid solubility of a molecule governs its entry into a cell

Carrier mediated transport

is a major contributor to transport into cells

Weakly basic drug

under acidic pH, solubility is increased and permeability is decreased

Weakly acidic drug

under acidic pH, solubility is decreased and permeability is increased

More charged weak acid at pH 9

less will go into the organic phase

More uncharged weak acid at pH 2

more will go into the organic phase

More charged weak acid at pH 2

less will go into the organic phase

More uncharged weak acid at pH 8

more will go into the organic phase

Excipients

Enhance dissolution, control release, extend stability

• diluents

• disintegrating agents

• chemical stabilizers

• surfactants

• lubricants

Dissolution experiments

should be conducted using conditions that mimic the environment in the gastrointestinal tract

Dissolution Rate (mg/min)

(Amttn+1 - Amttn)/(tn+1 - tn)

Case I

high solubility - high permeability drugs

Case II

low solubility - high permeability drugs

Case III

high solubility - low permeability drugs

Case IV

low solubility - low permeability drugs

dC/dt

is known as the dissolution rate

Cs

is the solubility of the drug in the stationary layer