Assay of Alkaloid and Amine Drugs

ASSAY ASSA Y OF ALKALOID AND AMINE DRUGS ALKALOIDS

1. Obtained from plant, animal and synthetic sources 2. Contain organic nitrogen(s) within their chemical structure 3. Possess physiological actiity !"#"$%& P$'#C'P&" 1.) Class of medicinal agents 2.) light deficiency of alaloid 3.) light e*cess %%+ O %&-%&O'%& $/! %# P$"P%$%0'O# 1.tandardiation 2.Proof of purity 3.Commercial ealuation Pharmacolegal purposes "04O 1. !raimetric 2. 5olumetric 3. pectrometric 6. "lectrometric 7. Physiological 0he amount of alaloids in a crude drug hae considerable ariation in different samples of the same drug. 5ariations is caused by seeral factors8 1. 0he age of the plant collected 2. eason of the year when the drug harested 3. oil and climate where the drug grown 6. Conditions under which the drug is collected, dried and stored 9uantity of alaloids present in !alenical preparations is also sub:ect to ariations 1. 9uality of drug employed 2. enstruum used in the e*traction of the alaloid 3. %mount of decomposition of the alaloid during the process of e*traction and storage eterioration of alaloidal preparation8 1. #ature of the alaloid 2. p4 alue of preparation 3. heat 6. light Principle inoled in ;uantitatie determination of alaloids by chemical methods8 (based upon physical and chemical properties of the substance) P4+'C%& P$OP"$0'" O&/<'&'0+ 1. %laloids ($3#) or free alaloids =sparingly soluble8 water =soluble8 most organic solents 2. %laloidal salts =soluble8 water =sparingly soluble8 immiscible solents C4"'C%& P$OP"$0'" $"%C0'O# '# %C' %# <%" 1. %laloids %laloids combine directly with acids to form salts 2. %laloids are liberated from a;ueous solutions of their salts by alalis 3. %laloids form highly insoluble precipitates with a considerable number number of reagents O/$C" O "$$O$

1. ailure to secure complete e*traction of the alaloids from the drug or from solution 2. &oss of olatile solent during maceration of the drug before the ali;uot portion is taen 3. 'mperfect separation of the immiscible li;uids 6. ailure to wash the stems of separators and funnels, graduates and other apparatus with solent 7. ecomposition of the alaloids >. /se of the wrong indicator ?. Other sources of error C4O'C" O '#'C%0O$ O$ %&-%&O'%& 0'0$%0'O# 'n alaloidal assays by olumetric methods, the use of methyl red solution is recommended in all the titrations. %&-%&O'%& 0"0 O&/0'O# 1. %uric chloride 2. Platinic chloride 3. ercuric chloride 6. !allotannic acid 7. Picric acid >. Phosphomolybdic acid ?. Potassium mercuric iodide @. ercuric iodide A. 'odine potassium iodide "$C/$'C 'O'" 0 (5alserBs reagent) =forms white precipitates with minute traces of many alaloids when it is added to their acidified a;ueous solutions 'O'#" 0 (agnerBs reagent) =yields reddish or red=brown precipitates of comple* composition with nearly all alaloids. 0he precipitates are usually amorphous. 0he ;uantity of reagent used should not be sufficient to color the solution more than a faint yellow. "$C/$'C PO0%'/ 'O'" 0 (ayerBs reagent) =yields white or slightly yellow precipitates when mi*ed with dilute solutions of many alaloids ragendorffDs reagent =yields an orange or orange red precipitate %%+ P$OC"/$" O$ O%!" O$ O %&-%&O' %# O04"$ %'#" $/! 2 ma:or steps8 1. eparation and collection of the amine or alaloid from other constituents found in the dosage form 2. %nalysis of the alaloid or amine by a suitable analytical method 04"O$+ O "E0$%C0'O# %ccording to #"$#0B &% if two practically immiscible solent are in contact and a substance soluble in both li;uids is added to them, the substance will distribute itself between the li;uids in such a way that the ratio of the concentrations of the two solutions is a constant irrespectie of the ;uantity of solute taen. 0his constant is ariously turned the distribution ratio, distribution constant, distribution coefficient, or partition coefficient. COP/0%0'O#8 -F C2C1  where in8 C1= concentration of alaloid in ether C2= conc. Of the same alaloid in e;ual olume -= distribution constant or coefficient %ssume that 1 g of atropine in 1GG ml of ether solBn when shaen with an e;ual olume of dilute 42O6 distributes itself so that G.1g remains in the ether layer and G.A g in the acid layer of the solent Hin maing successie e*tractions using e;ual olume of e*tracting solents, the following e;uation is useful in determining the ;uantity of solute remaining after n e*traction. O$/&%8  where

Wn

=W  (

¿ V  )n  KV  + V  1

2

2

=

 K 

c2 C 1

C2F concentration of solute in the e*tracting solent (2)

C1F concentration of solute in the original solent (1) F weight of solute originally taen nF weight of solute remaining in the original solent after n e*tractions 52 and 51F olume of solents 2 and 1,respectiely nF number of e*tractions P$OE'%0" %# /&0'%0" %%+ ='f the percent of e*tractie represents the total of a class of plant principles, such as alaloids or glycosides, etc., the assay is referred to as a pro*imate assay. e.g. the assay of ipecac ='f the percent of e*tractie from a crude drug represents a single chemical species, such as morphine, the assay is referred to as an ultimate assay. e.g. the assay of opium %%+ O C$/" $/! %# !%&"#'C%& %ssay of belladonna leaf &/'"E0$%C0 =