Levofloxacin Hemihydrate

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PURPOSE:-

To describe Raw material testing procedure of Levofloxacin Hemihydrate.

SCOPE:-

This procedure pertains to testing of Levofloxacin Hemihydrate.

Molecular Weight:-

370.38 g/mol

Chemical Structure:-

Levofloxacin Hemihydrate
Levofloxacin Hemihydrate

IUPAC NAME:-

(3S)-9-Fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid hemihydrate

RESPONSIBILITY:-

It is the responsibility of Analyst to follow this procedure while performing testing.

It is responsibility of Supervisor to make certain that this procedure is followed in its entirety.

It is responsibility of Manager to review and make changes where applicable.

EQUIPMENTS / INSTRUMENTS:-

HPLC

FTIR

Muffle Furnace

L.O.D Apparatus

MATERIALS / CHEMICALS:-

Dimethyl sulfoxide

Acetic Acid

Distilled Water

Acetone

Methanol

Glycerin

Octanol

Cupric Sulfate Pentahydrate

L-Ammonium Acetate

L-Isoleucine in Water

Methanol 

DESCRIPTION (USP)

Light yellowish white to yellow white crystals or powder.

CONTENTS:-

Contents are 98.0% to 102.0 %

SOLUBILITY (USP)

Sparingly soluble in water, acetone and methanol.

Soluble in Dimethyl sulfoxide and acetic acid.

Practically insoluble in Glycerin and octanol.

IDENTIFICATION BY FTIR SPECTROPHOTOMETER:-

Measure the FTIR spectra of sample and compare with standard.

The Retention time of the major peak of the sample solution corresponds to the standard solution as obtained in the assay.

QUANTITATIVE ASSAY

PROCEDURE:-

Preparation Of Buffer:-

8.5 mg/Litr ammonium acetate

1.25 grm/ Litr of Cupric Sulfate Pentahydrate

1.3 grm/Litr of L-Isoleucine in water

Preparation Of Mobile Phase:

Methanol and Buffer ( 3:7 )

Preparation Of Standard Solution:

Weigh 50mg of the Levofloxacin Hemihydrate RS and transfer it into 50ml of volumetric flask. Add mobile phase in it and sonicate to dissolve. Then make the volume up to the mark. Then filter the solution.

Preparation Of Sample Solution:-

Weigh 50mg of the Levofloxacin Hemihydrate (Raw Material) and transfer it into 50ml of volumetric flask.  Add mobile phase in it and sonicate to dissolve. Then make the volume up to the mark. Then filter the solution.

Chromatographic Conditions

Column        :           4.6mm x 25cm x Packing L1

Detector       :           UV at 360nm

Column Temperature :        45°C

Flow Rate    :           0.8ml/Min

Injection Size:          25µL

CALCULATIONS:-

Calculate the Percentage of  Levofloxacin Hemihydrate by using following Expression.

Where

ru = Peak Response from the sample solution

rs =  Peak Response from the standard solution

Cs = Concentration of Levofloxacin Hemihydrate in th standard solution (mg/ml)

Cu =   Concentration of Levofloxacin Hemihydrate in th sample solution (mg/ml)

P= Potency of Standard

 

L.O.D:-

2.0%  – 3.0% 

OPTICAL ROTATION:-

Solvent methanol

50mg/ml in solvent.

92° – 106° at 20°C

REFERENCE DOCUMENTS

United State Pharmacopeia, USP 41,NF 36, Volume III, Page No.2395-7. for Levofloxacin

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  1.  Amoxicilline Hydrate                 2.  Vitamin-C

 

Nitric Acid

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NITRIC ACID:

Commercially available HNO3 is an azeotrpe mixture with water. Mostly found in 68.0%. Nitric Acid is considered as strong acid.

CONTENTS:

63.0 %  m/m   to   70.0 %  m/m

Concentrated HNO3 is clear, colorless or almost colorless liquid, miscible with water

Having Density   =  1.384 g/cm3  to 1.416 g/cm3

A 10 g/L solution is strongly acid and give the reaction of nitrates

CHEMICAL STRUCTURE: 

Nitric Acid
Structure of Nitric Acid.

APPEARANCE:

Nitric acid is clear and not more intensely colored than reference solution

BOILING POINT:

120.5°C at 1 atm pressure

CHLORIDES:

Maximum 0.5ppm when 5 gram in 10 ml of water and 0.3 ml of silver nitrate and allowed to stand for 2 minutes protected from light any opalesense is not more intense than that of a standard prepared in the same manner using 13 ml of water, 0.5 ml of nitric acid, 0.5 ml of chloride solution and 0.3 ml of silver nitrate solution.

SILFATES:

maximum 2.0ppm

Evaporate 10.0 grams to dryness with 0.2 gram of sodium carbonate. Dissolve the Residue in 15 ml of distilled water. Prepare the standard using a mixture of 2 ml of sulphate standard solution and 13 ml of distilled water

ARSENIC:

Maximum 0.02ppm

Gently heat 50 grams with 0.5 ml of sulfuric acid until white fumes begin to evolve. To the Residue add 1 ml of a 100 g/L solution of hydroxylamine hydrochloride and dilute to 2 ml with water. Prepare the standard using 1.0 ml of arsenic standard solution

IRON:

Maximum 1.0 ppm

Dissolve the Residue from the determination of sulphated ash in 1 ml of dilute hydrochloric acid and dilute 250 ml with water and dilute 5ml of this solution to 10 ml with water

HEAVY METALS:

Maximum 2.0 ppm

Dilute 10 ml of the solution prepared for the limit test for iron to 20 ml with water. 12 ml of the solution complies with the test. Prepare the reference solution using Lead standard solution

SULFATED ASH:

Maximum 0.001%

Evaporate 100.0 grams to dryness moisten the residue with a few drops of sulfuric acid and heat to dull red.

ASSAY:

To 1.50 grams add about 50 ml of water and titrate with 1M Sodium Hydroxide using 0.1 ml of methyl red solution as indicator

1 ml of 1M Sodium Hydroxide solution is equivalent to 63.0mg of HNO3.

NITRIC ACID DILUTE:

(in dilute from it contains about 125g/L of HNO3)

Dilute 20 gram of HNO3 to 100 ml with distilled water

NITRIC ACID DILUTE R1:

Dilute 40 gram of HNO3 to 100 ml with water.

NITRIC ACID DILUTE R2:

Dilute 30 gram of HNO3 to 100 ml with water.

NITRIC ACID FUMING:

Fuming HNO3 contains 98.0% of HNO3 .It is clear, slightly yellowish liquid fuming on contact with air. Having density about 1.5 g/cm3. This grade is often used in explosive industry.

ANHYDROUS HNO3:

Anhydrous HNO3 contains 99.9% of HNO3. It contains maximum 2.0% of water and 0.5% of dissolved NO2. It is also known as White fuming nitric acid, pure nitric acid

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  1. Amoxicillin Hydrate        2.  Testing of Vitamin C in Drug

Amoxicillin Hydrate

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Amoxicillin

is a semisynthetic aminopenicillin antibiotic with bactericidal activity. It is used as Amixicillin Hydrate Amoxicillin binds to and inactivates penicillin-binding protein (PBP) 1A located on the inner membrane of the bacterial cell wall.

IUPAC  Name

IUPAC name of Amoxicillin Hydrate is

(2S,5R,6R)-6-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, trihydrate 

Molecular Formula

C16H19N3O5S • 3H2O

Chemical Structure

Amoxicillin
Amoxicillin Hydrate

Formula Weight

419.4 

Purity

≥98%

Physical Appearance:

Amoxicillin Hydrate occurs as white to light yellowish white, crystals or crystalline powder.

Solubility

It is slightly soluble in water and in methanol, and very slightly soluble in ethanol (96%).

Identification

Determine the infrared absorption spectrum of Amoxicillin Hydrate as directed in the potassium bromide disk method under Infrared Spectrophotometry , and compare the spectrum with the Reference Spectrum or the spectrum of Amoxicillin RS: both spectra exhibit similar intensities of absorption at the same wave numbers.

Optical rotation

＋290°   to   ＋315°

(0.1 g calculated on the anhydrous basis, water, 100 mL, 100 mm).

Heavy metals

To 1.0 g of Amoxicillin Hydrate add 2 mL of a solution of magnesium sulfate heptahydrate (1 in 4), mix, and heat on a water bath to dryness. Carbonize the residue by gently heating. After cooling, add 1 mL of sulfuric acid, heat carefully, then heat at 500°C – 600°C to incinerate. After cooling, add 1 mL of hydrochloric acid to the residue, and heat on a water bath to dryness. Then add 10 mL of water to the residue, and heat on a water bath to dissolve. After cooling, add ammonia TS to adjust the pH to 3 – 4, and add 2 mL of dilute acetic acid. If necessary, filter, wash the residue on the filter with 10 mL of water, transfer the filtrate and washings into a Nessler tube, add water to make 50 mL, and use this solution as the test solution. Prepare the control solution as follows:

To 2.0 mL of Standard Lead Solution add 2 mL of a solution of magnesium sulfate heptahydrate (1 in 4), then proceed in the same manner as for preparation of the test solution (not more than 20 ppm).

Water:

Not less than 11.0% and not more than 15.0%

(0.1 g, volumetric titration, direct titration).

Assay

Weigh accurately an amount of Amoxicillin Hydrate and Amoxicillin RS, equivalent to about 30 mg (potency), dissolve each in a solution of boric acid (1 in 200) to make exactly 100 mL, and use these solutions as the sample solution and standard solution. Perform the test with exactly

10 mL each of the sample solution and standard solution as directed under Liquid Chromatography according to the following conditions, and calculate the peak areas, AT and AS, of amoxicillin in each solution.

Amount [µg (potency)] of amoxicillin (C16H19N3O5S)

 

＝ MS × AT/AS × 1000

MS = Amount [mg (potency)] of Amoxicillin RS taken

Operating conditions:

Detector:

An ultraviolet absorption photometer (wavelength: 230 nm).

Column:

A stainless steel column 4.6 mm in inside diameter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 µm in particle diameter).

Column temperature:

A constant temperature of about 25°C.

Mobile phase:

Dissolve 1.361 g of sodium acetate trihydrate in 750 mL of water, adjust to pH 4.5 with   acetic acid, and add water to make 1000 mL. To 950 mL of this solution add 50 mL of methanol.

Flow rate:

Adjust so that the retention time of amoxicillin is about 8 minutes.

System performance:

When the procedure is run with 10 µL of the standard solution under the above operating conditions, the number of theoretical plates of the peak of amoxicillin is not less than 2500.

System repeatability:

When the test is repeated 6 times with 10 µL of the standard solution under the above operating conditions, the relative standard deviation of the peak area of amoxicillin is not more than 1.0%.

Containers and storage Containers:

Tight containers at Room temperature

Stability

≥ 2 years

Note before using Amoxicillin Product:

Do not use this medication if you are allergic to amoxicillin or to any other penicillin antibiotic, such as ampicillin, dicloxacillin, oxacillin, penicillin, and others.

Before using amoxicillin, tell your doctor if you are allergic to cephalosporins such as Omnicef, Cefzil, Ceftin, Keflex, and others. Also tell your doctor if you have asthma, liver or kidney disease, a bleeding or blood clotting disorder, mononucleosis (also called “mono”), or any type of allergy.

Amoxicillin can make birth control pills less effective. Ask your doctor about using a non-hormone method of birth control (such as a condom, diaphragm, spermicide) to prevent pregnancy while taking this medicine. Take this medication for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Amoxicillin will not treat a viral infection such as the common cold or flu. Do not share this medication with another person, even if they have the same symptoms you have.

Antibiotic medicines can cause diarrhea. This may happen while you are taking amoxicillin, or within a few months after you stop taking it. This may be a sign of a new  infection. If you have diarrhea that is watery or bloody, stop taking this medicine and call your doctor. Do not use anti-diarrhea medicine unless your doctor tells you to.

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  1.    EDTA          2.  Diclofenac Sodium            3.   Vitamin “C”

Testing of Vitamin “C” in a drug

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Here is the titration method for testing of Vitamin “C “in a supplement drug. It becomes more difficult to test Vitamin “C” in drug having Other vitamins like Vitamin “A “, Vitamin “E ” Vitamin B”, extracts like Ginkobiloba or Gensing and minerals like Zinc, or Seinite etc. So here is easy method to test the Vit. “C” in that drug.

PROCEEDURE: 

In the test , 1,2-diphenol-indophenol and metaphosphoric-acetic acid are used. first of all we are going to prepare both of these.

PREPARATION OF 1,2-diphenol-indophenol

Weigh 25mg of 1,2-diphenol-indolphenol in 100ml volumetric flask. add 25 ml of water and mix the weighed quantity. Now weigh 50mg of Sodium by carbonate and add in the mixture. add more 25ml of water and dissolve the reagents by continuous stirring by any mechanical means or  electromagnetic source.  and in last make the volume upto the marks using water.

PREPARATION OF Metaphosphoric Acetic-Acid

In a 100ml volumetric flask, Add 3ml of conc. phosphoric acid and 8ml of glacial acetic acid and makeup the volume upto the mark using distilled water. 

ASSAY OF VITAMIN “C”

Weigh accurately the product equivalent to 100mg of Vitamin C in 200ml volumetric flask. add 70ml of metaphosphoric acetic-acid in flask and sonicate for 30 minutes. Then makeup the volume upto the mark using distilled water. Mix the solution for 5 minutes and filter through whattman filter paper. or centrifuge some solution. take 4ml of the solution in a 100ml conical flask and add 5ml of metaphosphoric acetic acid. Now titrate with 1,2-diphenol-indophenol until rose pink color . 

each ml of 1,2-diphenol-indophenol used is equivalent to 0.136mg of Vit.C.

 

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Disodium Edetate ( EDTA )

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DISODIUM EDETATE: (EDTA)

Ethylenediaminetetraacetic acid (EDTA) is the aminopolycarboxylic acid. It is the disodium salt form of edetate, a polyvalent chelating agent with anti-hypercalcemic and anti-arrhythmic properties. Edetate, a heavy metal chelating agent, forms soluble stable complexes which are readily excreted by the kidneys, thereby can be used to lower serum calcium concentrations. Disodium edetate is used as a chelating agent in a wide range of pharmaceutical preparations, including mouthwashes, ophthalmic preparations, and topical preparation, typically at concentrations between 0.005 and 0.1 % w/v. Disodium edentate is also used as a water softener as it will chelate calcium and magnesium ions present in hard water.

IUPAC NAME OF EDTA:

disodium;2-[2-[carboxylatomethyl(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetate

OTHER NAME:

Disodium Edetate, EDTA disodium salt, 139-33-3, Titriplex III, Edta disodium, Disodium EDTA, Disodium salt of EDTA, Chelest B, Komplexon III, Clewat N, Disodium edathamil, Disodium edta, anhydrous, Zonon D, Dotite 2NA, Selekton B2, Tetracemate disodium, Cheladrate, Mavacid ED4, Versonol 120, Ethylenediaminetetraacetic acid disodium salt, Chelest 200, Disodium versene, Endrate disodium, Sodium versenate, Metaquest B, Kiresuto B, Veresene disodium salt, Chelaplex III, Complexon III, Diso-Tate, Chelaton III, Versene NA, Ethylenediaminetetraacetic acid, disodium salt,Triplex III, Chelaton 3

CHEMICAL FORMULA:

C10H14N2Na2O8

MOLECULAR WEIGHT:

336.21 g/mol

CHEMICAL STRUCTURE:

PHYSICAL APPEARANCE:

It is white crystalline powder, having melting point 240°C and boiling point 252°C.

SOLUBILITY AND pH:

It is soluble in water having pH 5.3

MANUFACTURING PROCESS:

All of the industrially used methods of manufacture of Disodium Edetate and its salts involve the addition of formaldehyde and hydrogen cyanide or an alkali metal cyanide to an aqueous solution of Disodium Edetate. The salts, or edetates, are then formed by hydrolysis. Disodium Edetate can also be formed by heating tetrahydroxyethylethylenediamine with sodium or potassium hydroxide using a cadmium oxide catalyst. Disodium EDTA was prepared by dissolving Disodium Edetate into a hot solution that contained two equivalents of sodium hydroxide. The solution was then allowed to crystallize.

HOW TO PREPARE 0.1M DISODIUM EDETATE (EDTA) :

Dissolve 37.5g of Sodium Edetate in 500ml water. Add 100ml of 1M Sodium Hydroxide and mix. Now dilute the solution to 1000ml with water.

HOW TO STANDARDIZE 0.1M DISODIUM EDETATE(EDTA):

Dissolve 0.120g of Zinc in 4ml of Hydrochloric acid. Add dilute sodium hydroxide solution until the solution is weakly acid. Now carry out the assay of zinc by complexometry. 1ml of 0.1M Disodium Edetate is equal to 6.538mg if Zinc.

HOW TO PREPARE 0.05M DISODIUM EDETATE(EDTA):

Dissolve 18.6g of Disodium Edetate in sufficient water to produce 1000ml.

HOW TO PREPARE 0.02M DISODIUM EDETATE(EDTA):

Dissolve 7.444g of Disodium Edetate in sufficient water to produce 1000ml.

HOW TO PREPARE 0.01M DISODIUM EDETATE:

Dissolve 3.722g of Disodium Edetate in sufficient water to produce 1000ml.

 

Mohr’s Method of Precipitation Titration

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MOHR’S METHOD OF DETERMINATION OF CHLORIDES BY TITRATION WITH SILVER NITRATE

Chem Pharma

is one of the oldest titration methods still in use – it was researched and published by Karl Friedrich Mohr in 1856.The idea behind this titration is very simple – chlorides are titrated with the silver nitrate solution in the presence of chromate anions. End point is signaled by the appearance of the red silver chromate.

Intense yellow color of chromate may make detection of first signs of formation of red silver chromate precipitation difficult. As some excess of silver must be added before precipitate starts to form, if concentration of titrant is below 0.1M, we may expect significant positive error. To correct for this error we can determine a blank, titrating a solution of the indicator potassium chromate with standard silver nitrate solution. To make result more realistic we can add small amount of chloride free calcium carbonate to the solution to imitate the white silver precipitate.
Solution during titration should be close to neutral. In low pH silver chromate solubility grows due to the protonation of chromate anions, in high pH silver starts to react with hydroxide anions, precipitating in form of AgOH and Ag2O. Both processes interfere with the determination accuracy.
Exactly the same approach can be used for determination of bromides. Other halides and pseudo halides, like I- and SCN-, behave very similarly in the solution, but their precipitate tends to adsorb chromate anions making end point detection difficult.

Reaction

Reaction taking place during titration is
Ag + Cl¯  →   AgCl (s)

Sample size

Assuming 0.1M titrant concentration and 50 mL burette, aliquot taken for titration should contain about 0.12-0.16 g chloride anion (3.5-4.5 millimoles).

End point detection

Before titration small amount of sodium or potassium chromate is added to the solution, making its slightly yellow in color. During titration, as long as chlorides are present, concentration of Ag is too low for silver chromate formation. Near equivalence point concentration of silver cations rapidly grows, allowing precipitation of intensively red silver chromate which signalls end point. See precipitation titration end point detection page for more detailed, quantitative discussion.

Solutions used

To perform titration we will need titrant – 0.1 M silver nitrate solution, indicator – potassium chromate solution, and some amount of distilled water to dilute sample.

Procedure

Pipette aliquot of chlorides solution into 250mL Erlenmeyer flask. Dilute with distilled water to about 100 mL. Add 1 mL of 5% potassium chromate solution. Titrate with silver nitrate solution till the first color change.

Result calculation

According to the reaction equation

Ag Cl– → AgCl

silver nitrate reacts with chloride anion on the 1:1 basis. That makes calculation especially easy – when we calculate number of moles of AgNO3 used it will be already number of moles of Cl– titrated. 

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if you want to read Accuracy and Precision then click on the Accuracy and Precision.

Accuracy and Precision

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Accuracy
In analytical chemistry, the term ‘accuracy’ is used in relation to a chemical measurement. The International Vocabulary of Basic and General Terms in Metrology (VIM) defines accuracy of measurement as… “closeness of the agreement between the result of a measurement and a true value.” The VIM reminds us that accuracy is a “qualitative concept” and that a true value is indeterminate by nature. In theory, a true value is that value that would be obtained by a perfect measurement. Since there is no perfect measurement in analytical chemistry, we can never know the true value.
Our inability to perform perfect measurements and thereby determine true values does not mean that we have to give up the concept of accuracy. However, we must add the reality of error to our understanding. For example, lets call a measurement we make XI and give the symbol µ for the true value. We can then define the error in relation to the true value and the measured value according to the following equation:
error = XI – µ   (14.1)
We often speak of accuracy in qualitative terms such a “good,” “expected,” “poor,” and so on. However, we have the ability to make quantitative measurements. We therefore have the ability to make quantitative estimates of the error of a given measurement. Since we can estimate the error, we can also estimate the accuracy of a measurement. In addition, we can define error as the difference between the measured result and the true value as shown in equation 14.1 above. However, we cannot use equation 14.1 to calculate the exact error because we can never determine the true value. We can, however, estimate the error with the introduction of the ‘conventional true value’ which is more appropriately called either the assigned value, the best estimate of a true value, the conventional value, or the reference value. Therefore, the error can be estimated using equation 14.1 and the conventional true value.
Errors in analytical chemistry are classified as systematic (determinate) and random (indeterminate). The VIM definitions of error, systematic error, and random error follow:
Error – the result of a measurement minus a true value of the measurand.
Systematic Error – the mean that would result from an infinite number of measurements of the same measurand carried out under repeatability conditions, minus a true value of the measurand.
Random Error – the result of a measurement minus the mean that would result from an infinite number of measurements of the same measurand carried out under repeatability conditions.
A systematic error is caused by a defect in the analytical method or by an improperly functioning instrument or analyst. A procedure that suffers from a systematic error is always going to give a mean value that is different from the true value. The term ‘bias’ is sometimes used when defining and describing a systematic error. The measured value is described as being biased high or low when a systematic error is present and the calculated uncertainty of the measured value is sufficiently small to see a definite difference when a comparison of the measured value to the conventional true value is made.
Some analysts prefer the term ‘determinate’ instead of systematic because it is more descriptive in stating that this type of error can be determined. A systematic error can be estimated, but it cannot be known with certainty because the true value cannot be known. Systematic errors can therefore be avoided, i.e., they are determinate. Sources of systematic errors include spectral interferences, chemical standards, volumetric ware, and analytical balances where an improper calibration or use will result in a systematic error, i.e., a dirty glass pipette will always deliver less than the intended volume of liquid and a chemical standard that has an assigned value that is different from the true value will always bias the measurements either high or low and so on. The possibilities seem to be endless.
Precision
The term precision is used in describing the agreement of a set of results among themselves. Precision is usually expressed in terms of the deviation of a set of results from the arithmetic mean of the set (mean and standard deviation to be discussed later in this section). The student of analytical chemistry is taught – correctly – that good precision does not mean good accuracy. However, It sounds reasonable to assume otherwise.
Why doesn’t good precision mean we have good accuracy? We know from our discussion of error that there are systematic and random errors. We also know that the total error is the sum of the systematic error and random error. Since truly random error is just as likely to be negative as positive, we can reason that a measurement that has only random error is accurate to within the precision of measurement and the more precise the measurement, the better idea we have of the true value, i.e., there is no bias in the data. In the case of random error only, good precision indicates good accuracy.
Now lets add the possibility of systematic error. We know that systematic error will produce a bias in the data from the true value. This bias will be negative or positive depending upon the type and there may be several systematic errors at work. Many systematic errors can be repeated to a high degree of precision. Therefore, it follows that systematic errors prevent us from making the conclusion that good precision means good accuracy. When we go about the task of determining the accuracy of a method, we are focusing upon the identification and elimination of systematic errors. Don’t be misled by the statement that ‘good precision is an indication of good accuracy.’ Too many systematic errors can be repeated to a high degree of precision for this statement to be true.
Significant figure
There are two types of significant figures, measured and exact.
Measured Observations
As scientists we get a large amount of the numbers we report, and use in our calculations from  measured observations. In this instance a number is determined to be significant or not by the accuracy and precision of the measuring device.  With a number derived from a measurement the last digit to the right  expresses the uncertainty.  For example if you are sure that your low resolution quadrupole mass spectrometer can deliver an accurate measurements to a tenth of a mass unit then you would be justified in reporting masses to a tenth of a mass unit.  For example if one measured a mass of 110.1 u this number would contain four significant figures with the last digit expressing the uncertainty.  The uncertainty would be plus or minus 0.05 u.  Even if the instrument could spit out 10 digits passed the decimal point one should only report the significant digits.  Errors can arise in calculations if insignificant figures are used in a calculation.  If a number resulting from a measurement is used in a calculation that involves multiplication or division all significant figures should be carried through the calculation and then the result should be rounded at the end of the calculation to reflect the term used in the calculation with the fewest significant figures. For example 10.4 X 5.0 should be reported as 52 and not 52.0.  If the calculation involves addition and subtraction a different rule applies, one should preserve common decimal places of the numbers involved.  For example if two numbers obtained from a measurement are used in an addition, 10.1 1000.234 the reported number should be 1010.3. Notice that 10.1 has 3 significant figures and 1000.234 has 7 significant figures and the result of the addition has 5 significant figures.
General rules for determining the number of significant figures in a number:
A) All non-zero numbers are significant.  
B) All zeros between significant numbers are significant, for example the number 1002  has 4 significant figures.
C) A zero after the decimal point is significant when bounded by significant figures to the left, for example the number 1002.0  has 5 significant figures.
D) Zeros to the left of a significant figure and not bounded to the left by another significant figure are not significant. For example the number 0.01 only has one significant figure.
E) Numbers ending with zero(s) written without a decimal place posses an inherent ambiguity. To remove the ambiguity write the number in scientific notation. For example the number 1600000 is ambiguous as to the number of significant figures it contains, the same number written 1.600 X 10^6 obviously has four significant figures.
Several Notes:
1)  It is important to know the accuracy and precision of the measuring device one is using and it is important to report only those digits that have significance. To reiterate, your electrospray mass spectrometer may be able to spit out 10 numbers past the decimal place but you should only use the digits that have significance in reporting or in a calculation.
2) It is generally accepted that the uncertainty is plus or minus 0.5 unit at the level of the uncertainty, for example the “true value” for the number 0.003 can be described as being bounded by the numbers 0.0025 and 0.0035.  It is important to note that in some instances scientists will want to express an uncertainty that exceeds 1 at the level of the uncertainty and this should be noted explicitly in the following fashion, 0.003 ± 0.002
Exact Numbers
Exact numbers are those that are counted without ambiguity, for example the number of mass spectrometers in the lab is exactly three, or the number of cars in the parking lot is exactly four.  These numbers carry no ambiguity and can be considered to have an infinite number of significant figures.  When using these numbers in a calculation the restriction on reporting is borne by the measured number if any.

Methods of Minimizing Errors

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Minimizing Systematic Error
Systematic error can be difficult to identify and correct. Given a particular experimental procedure and setup, it doesn’t matter how many times you repeat and average your measurements; the error remains unchanged. No statistical analysis of the data set will eliminate a systematic error, or even alert you to its presence. Systematic error can be located and minimized with careful analysis and design of the test conditions and procedure; by comparing your results to other results obtained independently, using different equipment or techniques; or by trying out an experimental procedure on a known reference value, and adjusting the procedure until the desired result is obtained (this is called calibration). A few items to consider:
What are the characteristics of your test equipment, and of the item you are testing? Under what conditions will the instrument distort or change the physical quantity you are trying to measure? For example, a voltmeter seems straightforward enough. You hook it up to two points in a circuit and it gives you the voltage between them. Under conditions of very low current or high voltage, however, the voltmeter itself becomes a significant part of the circuit, and the measured voltage may be significantly altered. Similarly, a large temperature probe touched to a small object may significantly affect its temperature, and distort the reading.
Check that any equations or computer programs you are using to process data behave in the way you expect. Sometimes it is wise to try a program out on a set of values for which the correct results are known in advance, much like the calibration of equipment described below.
It is unusual to make a direct measurement of the quantity you are interested in. Most often, you will be making measurements of a related physical quantity, often several times removed, and at each stage some kind of assumption must be made about the relationship between the data you obtain and the quantity you are actually trying to measure. Sometimes this is a straightforward conversion process; other cases may be more subtle. For example, gluing on a strain gauge is a common way to measure the strain (amount of stretch) in a machine part. However, a typical strain gauge gives the average strain along one axis in one particular small area. If it is installed at an angle to the actual strain, or if there is significant strain along more than one axis, the reading from the gauge can be misleading unless properly interpreted.
Calibration: Sometimes systematic error can be tracked down by comparing the results of your experiment to someone else’s results, or to results from a theoretical model. However, it may not be clear which of the sets of data is accurate. Calibration, when feasible, is the most reliable way to reduce systematic errors. To calibrate your experimental procedure, you perform it upon a reference quantity for which the correct result is already known. When possible, calibrate the whole apparatus and procedure in one test, on a known quantity similar in size and type to your unknown quantities.
Methods of minimization –
Gross errors cannot be completely eliminated, but can be minimized by taking proper care in reading and recording of the measurement parameter. One should, therefore, not be completely dependent on a single reading
Instrumental Systematic errors can be avoided by
a. selecting a suitable instrument for the particular measurement applications
b. applying correction factors after determining the amount of instrumental error
c. calibrating the instrument against a standard
Environmental Systematic errors can be avoided by air conditioning, hermetically sealing certain components in the instruments, and using magnetic shields
Observational Systematic errors can be avoided by concentrating on one particular measurement process at a time. Clearing out the area where the instrument is placed will also help the observer focus
Random errors can be treated mathematically using laws of probability. The idea is to repeat the measurement to gain high precision.

Pharmaceutical error and their types

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Pharmaceutical Errors


Pharmaceutical mistakes cause more than one million serious injuries or deaths in the United States each year. Pharmaceutical errors are generally preventable, and they can result in a type of medical malpractice lawsuit. A pharmaceutical error can happen at any point in the prescription process from the time the medication is picked to the time the medication is dispensed. Most often, the error is by a nurse or doctor, but at times a pharmacist makes a mistake in filling or dispensing the prescription. Some errors happen at retail chain drug stores and prescription mail order houses.
The Food and Drug Administration (FDA) reviews medication error reports from drug manufacturers and MedWatch. According to the FDA, the most common error resulting in a fatality was the administration of an improper dose of medicine. These accounted for 41% of fatal medication errors, whereas giving the wrong drug or using an improper type of administration resulted in 16% of medication errors.


Preventing Pharmaceutical Errors


It is important for patients to pay close attention to what their doctor or pharmacist tells them about the drug they are taking, the correct dosage, and any dangerous side effects. A patient should ask questions if there is any aspect of the instructions that he or she does not understand. Patients should tell doctors the names of all prescription drugs, over-the-counter pharmaceuticals, and herbal or vitamin supplements they are taking to avoid potentially dangerous interactions between pharmaceuticals.
The Division of Medication Error Prevention and Analysis (DMEPA) reviews reports of medication errors, defined as any preventable event that could lead to inappropriate medication use or patient harm. The error may arise when the wrong pharmaceutical or the wrong dose is prescribed or instructed on the label, or when the pharmaceutical interacts improperly with other drugs.


Recover Damages for Medication Errors


A bad reaction to a medication is not necessarily a pharmaceutical error. Instead, the error must be preventable to be actionable. A pharmaceutical error must also be the actual and proximate cause of a real injury to be actionable. A patient cannot sue for a pharmaceutical error that does not result in any actual harm.
Doctors must understand their patients’ conditions in order to avoid complications or dangerous drug interactions. A doctor owes a duty to advise a patient of any drug risks so that an informed decision can be made. When a doctor fails to relay a warning to a patient, he or she will have responsibility for the error. Similarly, a doctor can also be held liable for prescribing the wrong medication, prescribing the wrong dose, or failing to notice that a patient has an allergy to an ingredient in the medication.
A patient who suffers an injury from a pharmaceutical error also can bring a medical malpractice case against a nurse, pharmacist, or hospital that makes a mistake in filling or dispensing the medication. When a pharmacist gives the wrong instructions to a patient, dispenses the wrong medication, or mixes medications that should not be mixed, he or she also can be held liable for malpractice.
Among the damages that a plaintiff may recover are past and future medical expenses, lost earnings, loss of enjoyment, pain and suffering, and loss of consortium. Depending on the state, a plaintiff’s noneconomic damages may be capped by tort reform laws. If a patient dies due to a pharmaceutical error, his or her loved ones may be able to pursue a wrongful death lawsuit.


Classification of Errors:


Errors are classified in two types – Systemic (Determinate) and Random (Indeterminate) errors


Systemic (Determinate) errors:


Errors which can be avoided or whose magnitude can be determined is called as systemic errors. It can be determinable and presumably can be either avoided or corrected. Systemic errors further classified as
Operational and personal errorInstrumental errorErrors of methodAdditive or proportional error


Operational and personal error:


Errors for which the individual analyst is responsible and are not connected with the method or procedure is called as personal errors e.g. unable to judge color change
When errors occur during operation is called as operational error e.g. transfers of solution, effervescence, incomplete drying, underweighting of precipitates, overweighing of precipitates, and insufficient cooling of precipitates. These errors are physical in nature and occur when sound analytical techniques is not followed


Instrumental and Reagent errors:


Errors occur due to faulty instrument or reagent containing impurities e.g. un-calibrated weights, un-calibrated burette, pipette and measuring flasks.


Errors of Method:


When errors occur due to method, it is difficult to correct. In gravimetric analysis, error occurs due to Insolubility of precipitates, co-precipitates, post-precipitates, decomposition, and volatilization.
In titrimetric analysis errors occur due to failure of reaction, side reaction, reaction of substance other than the constituent being determined, difference between observed end point and the stoichiometric equivalence point of a reaction.


Additive or proportional errors:


Additive error does not depend on constituent present in the determination e.g. loss in weight of a crucible in which a precipitate is ignited.
Proportional error depends on the amount of the constituent e.g. impurities in standard compound.


Random Errors:
It occurs accidentally or randomly so called as indeterminate or accidental or random error. Analyst has no control in this error. It follows a random distribution and a mathematical law of probability can be applied.

Alcohol Number Determination

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Alcohol Number Determination represents the number of milliliters of ethanol at 15°C obtained from 10mL of tincture or other preparations containing ethanol by the following Methods.

A: Method 1 (Distilling method)

This is a method to determine the Alcohol Number by reading the number of milliliters of ethanol distillate at 15°C obtained from 10 mL of a sample measured at 15°C by the following procedures.

  1. Apparatus

Use hard glass apparatus as illustrated in figure Ground glass may be used for the joints.

  1. Reagent

Alkaline phenolphthalein solution: To 1 g of phenolphthalein add 7 mL of sodium hydroxide TS and water to make 100 mL.

  1. Procedure

Transfer 10 mL of the sample preparation, accurately measured at 15 ± 2°C, to the distilling flask A, add 5 mL of water and boiling chips. Distil ethanol carefully into the glass-stoppered, volumetric cylinder D. A suitable volume of distillate (mL) should be collected, according to the content of ethanol in the sample preparation. Prevent bumping during distillation by rendering the sample strongly acidic with phosphoric acid or sulfuric acid, or by adding a small amount of paraffin, beeswax or silicone resin before starting the distillation.

Chem Pharma

The figures are in mm

A: distilling flask (50ml)

B: delivery tube

C: Condenser

D: Glass stoppered volumetric cylinder (25ml graduated in 0.1ml)

When the samples contain the following substances, carry out pretreatment as follows before distillation.

(i) Glycerin: Add sufficient water to the sample so that the residue in the distilling flask, after distillation, contains at least 50% of water.

(ii) Iodine: Decolorize the sample with zinc powder.

(iii) Volatile substances: Preparations containing appreciable proportions of essential oil, chloroform, diethyl ether or camphor require treatment as follows.

Mix 10 mL of the sample, accurately measured, with 10 mL of saturated sodium chloride solution in a separator, add 10 mL of petroleum benzin, and shake. Collect the separated aqueous layer. The petroleum benzin layer was extracted with two 5 mL portions of saturated sodium chloride solution. Combine the aqueous layers, and distill. According to the ethanol content in the sample, collect a volume of distillate 2 to 3 mL more than that shown

(iv) Other substances: Render preparations containing free ammonia slightly acidic with dilute sulfuric acid. If volatile acids are present, render the preparation slightly alkaline with sodium hydroxide TS, and if the preparations contain soap along with volatile substances, decompose the soap with an excess of dilute sulfuric acid before the extraction with petroleum benzin in the treatment described in (iii).To the distillate add 4 to 6 g of potassium carbonate and 1 to 2 drops of alkaline phenolphthalein solution, and shake vigorously. If the aqueous layer shows no white turbidity, agitate the distillate with additional potassium carbonate. After allowing to stand in water at 15 ± 2°C for 30 minutes, read the volume of the upper reddish ethanol layer in mL, and regard it as the Alcohol Number. If there is no clear boundary surface between these two layers, shake vigorously after addition of a few drops of water, then observe in the same manner.

 

B: Method 2 (Gas chromatography)

This is a method to determine the alcohol number by determining ethanol (C2H5OH) content (vol%) from a sample measured at 15°C by the following procedures.

  1. Reagent

Ethanol for alcohol number: Ethanol (99.5) with determined ethanol (C2H5OH) content. The relation between specific gravity d15 of ethanol and content of ethanol (C2H5OH) is 0.797:99.46 vol% , 0.796:99.66 vol%, and 0.795:99.86 vol%.

  1. Preparation of sample solution and standard solution

Sample solution: Measure accurately a volume of sample at 15 ± 2°C equivalent to about 5 mL of ethanol (C2H5OH), and add water to make exactly 50 mL. Measure accurately 25 mL of this solution, add exactly 10 mL of the internal standard solution, and add water to make 100 mL.

Standard solution: Measure accurately 5 mL of ethanol for alcohol number at the same temperature as the sample, and add water to make exactly 50 mL. Measure accurately 25 mL of this solution, add exactly 10 mL of the internal standard solution, and add water to make 100 mL.

  1. Procedure

Place 25 mL each of the sample solution and the standard solution in a 100-mL, narrow-mouthed, cylindrical glass bottle sealed tightly with a rubber closure and aluminum band, immerse the bottle up to the neck in water, allowed to stand at room temperature for more than 1 hour in a room with little change in temperature, shake gently so as not to splash the solution on the closure, and allow to stand for 30 minutes. Perform the test with 1 mL each of the gas in the bottle with a syringe according to the Gas Chromatography

Under the following conditions, and calculate the ratios, QT and QS, of the peak height of ethanol to that of the internal standard.

Alcohol Number = \frac{Qt}{Qs}\times \frac{5mL}{a volume ml of sample}\times \frac{ethanol content(volume%)}{9.406}

Internal standard solution—A solution of acetonitrile (3 in 50).

Operating conditions—

Detector:  A hydrogen flame-ionization detector.

Column:  A glass tube about 3mm in inside diameter and about 1.5 m in length, packed with 150- to 180µm porous ethylvinylbenzene-divinylbenzene copolymer (mean pore size: 0.0075 µm, 500 – 600m2/g) for gas chromatography.

Column temperature: A constant temperature between 105°C and 115°C.

Carrier gas: Nitrogen.

Flow rate: Adjust so that the retention time of ethanol is 5 to 10 minutes.

Selection of column: Proceed with 1 mL of the gas obtained from the standard solution in the bottle under the above operating conditions, and calculate the resolution. Use a column giving elution of ethanol and the internal standard in this order with the resolution between these peaks being not less than 2.0.

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