An article on contamination of Diethylene Glycol in Pharmaceuticals. Thanks to Dr. Ajaz S. Hussain for all teaching, sharing knowledge and supporting in professional development.

1. DEG - A Bullet to blast the Kidney
Listen to the Voice of Silence – 2022 Gambia & Indonesia Tragedy - Another wakeup call
Roohi B. Obaid
Chief Executive Officer,
Center for Quality Sciences, 01 Nov 2022
roohibanoobaid@gmail.com
How unfortunate and saddened to know that 66 children died in Gambia, 99 died in Indonesia
reported a few weeks ago. All had taken cough syrup and entered in the Death Valley by primarily
suffering from acute kidney failure. These cough syrups were found contaminated with Di Ethylene
Glycol (DEG). Let us recall the historical tragic incidence of 1937 associated with it, when a sweet
in taste, but toxic industrial solvent was unintentionally used for the formulation of an antibiotic
medicine sulfanilamide elixir. This elixir instead of relieving infection ended up with deaths on a
large scale all around where it was supplied. Consumers were helplessly waiting for death, whether
adult or old or children. Likewise, authorities were trying their best to control the pressure of storm
by their hands, they succeeded to reduce the threshold of damages but could not save precious lives.
Everybody knows neither the drug (sulfanilamide) nor the dosage form (elixir) was responsible for
this catastrophe. Other than the ingredient known for desired therapeutic value, every ingredient
used to formulate finished dosage form is considered excipient and termed as inactive ingredient. It
was a solvent in this case that was recognized as inactive ingredient, even today too. It was the first
known incidence of DEG, not the last. This world witnessed dozens of mass poisoning since 1937
and every time we lost precious lives of consumers. Follow on incidences are not due to conscious
use of Di Ethylene Glycol in drug product but the contamination or mix up due to wilful ignorance
and deliberate negligence. Established clinical features of DEG poisoning are neurotoxic,
hepatotoxic and nephrotoxic. Dot of elevated cerebrospinal fluid protein concentrations in victims
of DEG may easily be connected with the obvious kidney injury. DEG converts into hydroxy ethoxy
acetic acid and promotes acidosis, that sharply targets kidney cells responsible for filtration and
thereafter creatinine is increased in blood to challenge the biochemical balance throughout the body
and brain.
Widely used solvent in pharmaceutical products such as Sorbitol, Glycerin and Propylene Glycol
(PG) have potential and tendency to be mixed or contaminated with DEG. Repetition of error may

2. not be excluded to recognize as commission of mistakes. Recent wave of DEG contamination is
nothing but a striking whistle for us to take a deeper insight on the issue. Determination of Lethal
Dose (LD) 50 and Effective Dose (ED) 50 for any substance are the fundamental interest of
researcher, corporate, government in drug products. Pursuance to know about the minimum
concentration of each poison that triggers toxicity is the first line towards safety, LD50 helps to
calculate it. As a matter of reality, we do not yet know what is the actual toxic concentration of DEG
causing irreversible damages? How ignorant and weak we are that we do not know why do we still
call it as inactive ingredient? Why have we not succeeded to develop a sensitive, rapid and
economical test method to detect DEG reliably from raw materials and finished goods. It is a matter
of serious concern that we rely on supplies without valid reason of trust for purity and subsequent
testing to detect DEG contamination. How do we know that the solvents we are using in
pharmaceutical manufacturing do not contain DEG as a contaminant is a big question on quality
system? It is a life-saving profession where emotion is an attribute in caring the patient. Complexity
in supplies no matter it is active or any excipient must not be subject to any insecurity. How do we
know that the Certificate of Analysis (CoA) or third party testing for confirmation of absence of
DEG is reliable? Do we know the prevalence of renal failures in pediatrics and the conclusive reason
for isolated or systematic cases? How we assure that such incidences will not happen here in Pakistan?
How can we continue to call it inactive while it is taking human lives heartlessly? Is it correct to
attribute this tragedy with cough syrup and sometimes with Paracetamol syrup?
As a matter of fact, DEG, Glycerin, PG etc. are widely used in other industries too. Suppliers are
probably not capable to understand harm of DEG contamination or mix up in supplies to
pharmaceutical industry. Cost difference (up to half dozen time) is significant between DEG and
PG or Glycerin, therefore intentional mix up probability in supply chain may not be ruled out.
Greed and protection from unwanted commercial interest on the cost of public health needs
appropriate monitoring and controls at every end. Imported Glycerin from China via a European
trader was found mixed with 24% DEG in 1995 and known as Haiti incidence. Another cough
expectorant manufactured in a company of India was found contaminated with DEG (17.5% v/v)
in 1998.
There was no mandate or obligation to perform test of DEG before 21st
century. Unluckily, neither
the corporate nor the authorities took interest to do so and it is important to note that academia is

3. not motivated enough to work on it. So far, scientific valid studies are limited to determine reliable
concentration that potentiates irreversible damage upon administration in humans. However,
findings of decades and different geographical evidences navigate that significant amount of DEG is
required to damage kidney, however valid studies are missing to conclude such important subject.
It is roughly calculated by the consumption of syrups from the bottles of victim who died from DEG
poisoning. Trace-back investigations following the 2006 outbreak of DEG-induced renal failure in
Panama found that imported raw material labeled glycerin and used by the Panamanian
pharmaceutical manufacturer in the cough syrup formulation contained 22.2% DEG. The worst
case of 339 deaths on use of Paracetamol syrup containing PG contaminated with DEG in 1990-92
occurred in Bangladesh. These contaminations of DEG could have been detected by Thin Layer
Chromatography (TLC) that has never been promoted. Simple and on-site detection techniques
based on valid TLC method for DEG are available to catch 6% DEG in Glycerin and 2% DEG in
Paracetamol elixir. However, staining the sheet permits detection of DEG at less than 0.1%. It is
little amazing that the method prescribed by the regulatory authority is more sensitive and high tech
(GC-MS) to detect 0.01% contamination. Emphasis on GC-MS is practically difficult case itself,
testing for each drum of glycerin or propylene glycol is another challenge. Absence of GC-MS facility
in pharmaceutical, nutraceuticals, over the counter (OTC) drug manufacturing industries and
supplier of unregulated consumer products becomes an excuse to waive the test and taking undue
risk. Proportional use of logic is the essence of safety by design. On the other hand, in absence of
test and presence of blind spots, it is difficult to connect acute kidney injury with this potential DEG
contamination for several reasons. Pharmacovigilance can be a great additional tool in identification
of real time data. If data is of integrity and managed on large scale, it can provide opportunity of
data mining corresponding to clinical cases and supply chain sampling studies for DEG. Historically,
it has been difficult to establish consistent measures of the incidence and prevalence of acute kidney
failure in pediatrics. In this time of uncertainty, we should discuss the subject among professionals
having real time experience based knowledge to respond, how does one can detect DEG associated
clinical spectrum progression of acute kidney failure?
Footnote: All information is widely available in public domain.