Structural Formula and Functional Groups of Drugs


All goods manufactured by human beings is subject to decomposition and all pharmaceutical drugs are no exemption to this. The activity function of all drugs changes with time and this rate of degradation are accelerated by external factors such as water moisture, oxygen and thermodynamic energy absorbed from the environment. The speed at which pharmaceutical drugs deteriorate differs considerably and for some drugs, if properly packaged and kept, can maintain integrity for even ten years, even though Food and Drug Authority advocates for a maximum of five years. Given that the assessment of drug steadiness is very important and needs highly level of expertise, the government has stepped in to regulate this exercise to ensure drug quality, safety and effectiveness is maintained (Carstensen & Rhodes, 2009, p. 3).

The mechanism and extend to which drugs decompose varies with the active ingredient and therefore the undesirable effects that these drugs can cause varies with individual drug. It should be noted that in most cases if any pharmaceutical drug has less than 90 percent of indicated active ingredient on the label, that product is deemed unfit for human use and therefore shelf-life should not allow any drug to fall below this range. Drugs are known to degrade via oxidation in presence of oxygen, hydroxylation in presence of water moisture and photo degradation in presence of direct lighting. For hydrolysis, this can be minimized by coating tablets with enteric coat and keeping drugs in cool dry places. On the other hand, oxidation can be minimized by maintaining an inert atmosphere and this is done by flushing the solution with inert gas such as neon or group eight elements prior to sealing the ampoule since this process occurs by free radical mechanism. We also reduce the chances of degradation appreciably by using colored packaging materials to protect the drug from heat in addition to single entity blister packaging (Carstensen & Rhodes, 2009, p. 4)

Importance of Stability Test

Drug stability tests are vital because it takes care of interests of the patients who use these drugs. Apart from worrying about loss of potency of these drugs once they degrade, this degradation can lead to harmful products with potential of causing death or other dangerous disease instead of healing, therefore stability test is very important. A stability test also serves to protect the reputation of the manufacturer and build confidence in drugs by patients (Carstensen & Rhodes, 2009, p. 4). Stability test also helps in building drug database that can be used as a reference point when developing other formulations in the future. In this discussion will the stability of Fentanyl, Pentazocine, Loperamide, Naloxone and Propoxyphene drugs and the kind of precautions that should be employed to minimize or prevent the degradation of the mentioned drugs due to hydrolysis oxidation/reduction (Connors & Amidon, 1986, p. 4).

Structural Formula and Functional Groups of Drugs

Chemical Structure Name Functional Groups
Formula Fentanyl Amide N
Benzyl ring
Formula Loperamide Dimethylamide moiety
α-phenyl ring and α -carbon in the piperidine ring
2,4-dihydroxy-4-(p-chlorophenyl) piperidine ring.
Formula Naloxone Allyl moeity
Formula Pentazocine C-3
Terminal methyl groups on N moeity
Formula Propoxyphene Dimethyl amino group
Formula Methadone Aminoalkyl group
Aminoalkyl group


This is an opioid pain killer known by its IUPAC name N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenyl-propanamide and is employed as a remedy for “breakthrough” cancer ache when other cancer drugs fails. Some of the drugs in which Fentanyl is an active ingredient include Duragesic, Actiq, Onsoli, and Instanyl among other drugs. This drug is almost 100 times greater in terms of effectiveness than morphine. It emerges that both the duration of action and effectiveness in the sequence of fentanyl analogs replaced in fourth position of the piperidine ring is controlled only by the steric condition and not by the chemical character of the substituent. Fentanyl is the prototype of the 4-anilidopiperidine class of synthetic opioid analgesics.

The products of degradation of Fentanyl are as follows: N-phenyl-1-(2-phenylethyl)piperidin-4-amine, 4-N-(N-propionylanilino) piperidine, 1-(2-phenethyl)-4-N-(N-hydroxypropionylanilino) piperidine (minor metabolite), 4-N-(N-hydroxypropionylanilino) piperidine, N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]acetamide and (1S,2R)-1-benzyl-3-(dimethylamino)-2-methyl-1-phenylpropyl acetate. Fentanyl citrate is not compatible with thiopental methohexital and sodium. Structurally, because of steric effect due to crowding of phenyl and piperidine rings coupled with introduction of water molecules in the ring leads to hydrolysis. This drug should be protected from light by using dark bottles or keeping them away from direct lighting (Long, 2009, p. 2).


This is a piperidine derivative known by its IUPAC name as 4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl] – N, N-dimethyl-2, 2-diphenylbutanamide. It is used to treat diarrhea caused by gastroenteritis. In many nations, it is traded under the brand names for example lopex and pepto. The products of deterioration or decomposition of a Loperamide are as follows: Desmethyl loperamide, 4-(p-chlorophenyl)-4-hydroxyl-N,N-dimethyl-α,α-diphenyl-1-piperidinebutyramide, Didesmethylloperamide, 4-[4-(4¢-chlorobiphenyl-4-yl)-4-hydroxypiperidin-1-yl]-N,N-dimethyl-2,2-diphenylbutanamide, 4-(4-chlorophenyl)piperidin-4-ol, loperamide oxide and 4-(4-hydroxy-4-phenylpiperidin-1-yl)-N,N-dimethyl-2,2-diphenylbutanamide. Structurally, there is repulsion among hydroxyl, 2, 4-dihydroxy-4-(p-chlorophenyl) and piperidine leading to weakening of covalent bonds among the molecules and this explains why the compound easily cleaves when exposed to light. For hydrolysis, we have water loving molecules such as hydroxyl group which will attract water molecules leading to hydroxylation of loperamide.

For Loperamide, do not dilute oral solution with other solvents and also the drug should be light by using dark bottles or keeping them away from direct lighting as this causes cleavage due weak intermolecular bonds between the functional group and parent compound.


The levo isomer of isomethadone and methadone are as twice active as its racemates and elimination of any of phenyl rings decreases the activity of the drug (MedicineNet, 2010, p. 1).. The functional groups responsible for drug activity and degradation include propanoyl and Aminoalkyl group. Decomposition of Methadone leads to the following products; isomethadone ketimine , 2-ethyl-3,3-diphenyl-5-methylpyrrolidine, 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine , (5RS)-6-(dimethylamino)-5-methyl-4,4-diphenylhexan-3-one (isomethadone) Diphenylacetonitrile, (3RS)-4-(dimethylamino)-3-methyl-2,2-diphenylbutanenitrile (isodidiavalo) and (4RS)-4-(dimethylamino)-2,2-diphenylpentanenitrile(isodidiavalo)

This hydroxylation is due heavy molecular weight of methadone and additional of water molecules to the structure plus electronic repulsion among molecules leads to decomposition of methadone. Also this degradation is a result of weak covalent bond between carbon-carbon bonds. When Methadone is exposed to light, the energy absorbed leads to decomposition therefore should be protected from light (Pharmaceutical Society of Australia, 1992, p. 2).


The functional groups responsible are as follows; Allyl moiety which undergoes reduction, C-6 is hydrolyzed and C-3 is oxidized. When Naloxone is exposed to light or water moisture, the compound degrades to the following compounds; Naloxone-3-glucuronide, 6-hydroxy product of naloxone, 3-O-allylnaloxone, 10a-hydroxynaloxone, N-allyl-14-hydroxy-7,8-dihydronormorphine-3-glucuronide and -didehydro-4,5a-epoxy-3,14-dihydroxy-17-(prop-2-enyl)morphinan-6-one (7,8-didehydronaloxone).

Molecularly, this is degradation is possible due to cis arrangement of molecules and repulsion between ethyl groups on the crowded nitrogen atom. Naloxone is sensitive to temperature variation and therefore should be stored between 15 and 30 °C. Additionally, the drug should not be frozen and must be kept in amber or dark bottles to avoid cleavage, oxidation and hydrolysis (American Chemical Society, 2010, p.4)


This is a synthetic prototypical drug known by IUPAC name as 2-dimethy​lallyl-5,​9-dimethy​l-2′-hydr​oxybenzom​orphan. The functional group responsible for hydroxylation is terminal methyl groups on N moiety and C-3 for oxidation. Pentazocine decomposes to Pentazocine -3-glucuronide and Hydroxyl derivative of Pentazocine. Any drug containing Pentazocine should be stored an airtight container to prevent it from being hydrolyzed and be protected from direct lighting (Carstensen, 1990, p. 3)


It is a narcotic cough suppressant and pain killer but less effective as compared morphine. The functional group responsible for oxidation is dimethyl amino group. The compound undergoes oxidation because when water molecules attaches to the amino group it causes steric constrain leading to breaking of weak intermolecular bonds leading to the following products: nordextropropoxyphene (norpropoxyphene), (1S,2R)-1-benzyl-3-(dimethylamino)-2-methyl-1-phenylpropyl acetate and (2S,3R)-4-(dimethylamino)-1,2-diphenyl-3-methyl-butan-2-ol. As a safety measure, it should be kept in airtight containers and be protected from light (Connors & Amidon, 1986, p. 5).

Reference List

American Chemical Society (2010). Medication and Drugs: Pentazocine, Web.

Carstensen J. (1990). Drug Stability: Principles and Practices. In: Drugs and the Pharmaceutical Sciences. Vol 43. New York: Dekker, 1990

Carstensen J. and Rhodes C. (2009). Drug Stability: Principles and Practices. Drugs and the Pharmaceutical Sciences. Vol 107. 3rd Ed. New York: Basel. Web.

Connors K. and Amidon G. (1986). Chemical Stability of Pharmaceuticals: A Handbook for Pharmacists. 2nd Ed. New York: Wiley

Long P. (2009). Internet Mental Health: Pentazocine. Drug Monograph. Web.

MedicineNet (2010). Medications and Drugs: Naloxone Health Information, Web.

Pharmaceutical Society of Australia (1992). Australian Pharmaceutical Formulary and Handbook. 15th ed. Canberra: Pharmaceutical Society of Australia