Flashcards in Medicine - Measurement and Data Reliability Deck (37):

1

## Name 5 steps in drug analysis

###
1) Take representative sample

2) Extract analyte(s) from interfering matrix

3) Separate analytes

4) Identify, detect and quantify analytes

5) Determine reliability/validity of results

2

## 5 Steps of analysing a sample

###
1) Select representative sample

2) Extraction -e.g. a lot of matrix is present

3) Purification - e.g. is the test highly susceptible to impurities, excipients, degradation products

4) Characterisation - the target analyte should be identified, especially if the test is not very specific

5) Data validity - us stats, comparison with standards and/or another method. If you are testing by a newly developed method or if the method has been changed significantly then it is critical to validate the new method first

3

## Ways to present and handle analytical data

###
-Can you group it? - frequency table - histogram if numerical or bar chart if numbers and text

-Did you change only one parameter? Line graph suitable where x axis having independent variable (what you altered) and y axis being dependent variable (what you measured)

-If you changed more than one variable then a scattergram may be suitable

4

## How to get the line of best fit?

###
Linear regression analysis - better than manual determination

equation of the line of best fit

y = a + bx

Use equation where:

a and b are parameters of the line

b is the slope, a is the y intercept

N= number of pairs of values

5

## Analytical measurements are not exact. What do we do in reaction to this?

### Assume the last digit quoted in a measured value is uncertain

6

##
An analyst weighs 25 tablets and finds the average weight per tablet.

Then he calculates that 38 tablets should weigh 44.2239672g. The accuracy of the balance is +/-0.1mg

How should he write the result?

### As Weight= 44.2240g

7

## When calculating drug content, how many significant figures is favoured for the answer?

### 3 significant figures

8

## Rules for sigfigs when adding or subtracting?

###
Round off to the same number of decimal places as the value having the fewest decimal places

e.g.

10 + 28.621 = 129

9

## Rules for sigfigs when multiplying or dividing?

###
Round off to have the same number of sig figs as the value with the least significant figures

e.g.

2.1 x 11.31 = 24

10

## How should one take measurement on a scaled instrument?

###
Go for one more figure than you can read with certainty

e.g.

Manufacturers often give accuracy value to their apparatus. A graduated 50ml burette may be accurate to only +/-0.02mL

Therefore when measuring 30ml of solvent you should report to this level of accuracy only as 30.00ml

11

## What 3 types of errors affect validity of analytical measurement?

###
1) indeterminate (random) error

2) determinate (systematic) error

3) Gross error

12

## What is indeterminate error and what does it affect?

###
Random error

Evaluate with statistics

affects precision more than accuracy

13

## what is determinate error? how to evaluate it?

###
Systematic error

evaluate with standards

affects accuracy more than precision

14

## Gross error is what?

### A big mistake, like spilling everything on the floor, sample evaporated etc. the value stands out as an outlier.

15

## What do random errors follow statistics wise?

###
The normal distributions or Gaussian pattern

16

## With the normal distribution, use standard deviations to explain how sure one can be where the values are

###
68% values within one sd (or 68% chance that random error will not exceed +/-1sd)

95% are within +/- 2sd

99.7% are within +/- 3sd

of the mean value

17

## What is precision?

###
How close (repeatable) the measurements are to each other

18

## How is precision expressed?

###
Range (quickest) - difference between highest and lowest results

Standard deviation or the relative standard deviation - preferred. Calculate by statistical analysis

19

## What is relative standard deviation?

###
The spread of data expressed as % of the mean value, so units become unimportant

+/- RSD also called the coefficient of variation (CV)

use RSD to remove units

divide by mean

20

## What is accuracy?

### how close the measurement is to the accepted value

21

## How can we evaluate accuracy?

###
by calculating the absolute error (measured value minus a true value)

and relative error

22

## Equation for absolute error

###
E=xi-xt

where xi= observed value and xt= true value

23

## Equation for relative error

###
E=(xi-xt)/xt * 100%

percentage value

24

## Name and describe 3 origins of systematic error

###
1) Instrumental

Calibration - apparatus (cylinders, dispensers etc) or equipment (balances, pH meter etc)

2) Method

Reagents (unstable), reactions (incomplete)

3) Personal error

e.g. eye sight (colour), height (can not read burette at eye level) etc

25

## What can a null hypothesis that assumes to bias verify?

### If a difference is due to a random or systematic error (bias) in the method or not

26

## When do you reject the null hypothesis?

###
If xbar-xt>+/-ts/SRN

where xbar = mean

xt = true value

SRN = square root of N

ts = standard deviation

27

## When do you accept the null hypothesis?

### xbar-xt

28

## What is t-Test?

###
One of the most powerful and widely used statistical tests

It is used to calculate the confidence intervals of a measurement when the population standard deviation is not known, which is the case with limited number of data points

29

##
What can the t test be used to do?

What does the t test correct for?

###
Used to compare two averages

Corrects for the uncertainty of the sample standard deviation caused by taking a small number of samples

30

## How to detect gross error?

###
use a Q test

You can use a Q distribution table to compare the Q experimental value at a given confidence level with Q critical value in the table

31

## Using the Q test, when is a value an outlier?

###
When Qexp>Qcritical

32

## Qexp=?

###
Qexp=(xq-xn)/w

where xq=value in doubt

xn=nearest value to doubted

w=range

33

## What is method validation?

### The process of demonstrating that analytical procedures are suitable for their intended use and that they support the identity, strength, quality, purity and potency of the drug substances and drug products

34

## In method validation, in addition to the details of how to carry out an assay (SOP) what else must the method state?

### How the sample is extracted/prepared or handled before it is analysed. Quality of reagents including reference or standard materials used. Procedures for instrument calibration, reagent preparation, method of sample preperation and handling

35

## When do methods require complete validation?

### When they are new methods

36

## When are pharmacopoeial methods not valid?

### If they are significantly changed. Any changes must be validated (partial validation)

37