Pharma

1)- HPLC –MS is used for the detection and identification of chemicals in a
complex mixture. The physical separation capabilities of HPLC and the mass
analytical capabilities make this process a more sensitive and selective technique.
(5)
The process of the pharamaceutical development in which this techniques is used
are as follows :- 1)- pharmacokinetic studies of pharmaceuticals .
2)- in drug development
3)- high throughput screening of the lead discovery compound
4)- during a chemical synthesis and formulation.
The Manufacturing Stage of a drug :-
 Identification test

The confirmation of the identity of the API inside the drug substance . A run of
the chromatogram is made against the profile of standard chemicals so obtained
from different sources. (1,3,4,9,10)
 Uniformity of content of the drug

A sample assay is done which quantitatively measures the real amount of the
APInt compared to that is expected to be . (1,3,4,9,10)
 Dissolution tests

The dissolution tests are performed to ca
y out (1) batch-to-batch quality of a drug
assessment ; (2) appraisal of new formulations and (3) ensure continuity in product
quality (1,3,4,9,10)
 Drug Impurities assessment

The API manufacturing process gives rise to many potential impurities such as ,
isomers, intermediates, reagents and reaction by-products . HPLC has become the
major analytical technique in this process. (1,3,4,9,10)
 Drug Stability test

Stability testing of drug substance is done to ensure the consistency in the qualitynt
with time due to the influence of different environmental factors such as
temperature, humidity, and light . (1,3,4,9,10)
The different advantages which is offered by this techniques are as follows :-
 “Specificity”
 “Accuracy”
 “Precision”
 “Linearity”
 “Range”
 “Detection Limit”
 “Quantitation Limit”
 Robustness
For quantitating the samples two procedures are required such as :-
1- HPLC by which the physical quantitation is done along with
2- MS by which the mass determination of the particular smaple is done .
2)- The mass spectrometer measures the mass/charge (m/z) ratio of the molecules
. Therefore, molecules must be ionized first before going into analysis .
• they must have a source of ionization . (7,8,13,15)








The working of the mass spectromete


The difference between Full scan MS and Single ion Monitoring MS
A MS system in “Full Scan mode” measures a range of mass to charge ratios (
m/z).This mode is useful for identification of the unknown compounds in a given
sample .(7,8,13,15)
The MS in a SIM mode works with increased sensitivity relative to “full scan
mode”.here the charge to mass ratio of the molecuels of specified interest is seen
minutely .in fact the sensitivity is increased by a factor of 10- 100 . (7,8,13,15)
The “precursor ions” are selected in the first mass analyzer rather than in the
second one . the product ions are selected in the second mass analyzer in which the
fragments specified by the user is measured in case of product ions .
3)-

QA – is defined as the processes in which the approval of the protocol, audits
ecords for compliance to SOPs is done .
QC - measures concentration of drugs and their metabolites in appropriate
iological matrix, reviews data, and reports results. Identifying the metabolites and
analyzing data for ADME is the responsibility of the metabolism group (20-26)
The drug approval process is time consuming and costly which makes it
impractical for pharmaceutical companies for applying to get the “NDAs” and
“ANDAs” for products with minor variations in dosages. (20-26)
Most of the compounded products are considered as more or less as unapproved
drugs due the deviation of their contents w.r.t their FDA-approved counterparts.
Thus without ca
ying out extensive research, to prescribe for compounded
products relies primarily on professional judgment . (20-26)
Many compounded products are used for a diverse kind of people such as
neonates, pediatric and geriatric patient those having different pharmacokinetic and
pharmacodynamic profiles from normal adults. The different Systemic agents such
as inhalation has a higher risks of microbial contamination if their processes are
not sterilely conducted . (20-26)
Compounding also involve change of the formulation of a commercially available
product as well as combination of active ingredients, also known as (API). (20-26)
4)-
QA organization must be established
•Training of Personnel
•Auditing of documentation
•Archiving of all records and data
•Job Descriptions
•Documented Processes and Procedures in place covering all sections of 21 CFR
Part 58 (19)
Management Team and Study Director
•A study director must be identified is responsible for all aspects of the study
design, evaluation, and reporting of the...