QI AClTV CONTROL DEPA RTMENT

""n;.J1";i f.'
•
j
­ r
; j, rm. PI ~

- ---------
STAND ARD TEST PROCEDURE
.,
fP ro'du ". Lmagii pt in
lLGP!STPIOO I103
Depa tm cnr QC ST P No.
o6! IOnU22
I Sup~~: les LGP/STP/OOI /02 P I'ep;lred 011

~Ilcth' ~derc n ce In -House

._ --
Effective Date
-_. 11/10/2022
~ ----.

1.0 Desc ript ion:

I akt about I g OneS! sample in a petri di sh and obs!.:'l'\!.: for color dlHl nmun:,

2.0 So lu bility:
'Solub le in Methylene dic hloride Very slight ly so!ub lt' in WaleI' ,~nu ISl)rropan nl.
Dissulve I g sample in 10 m L Methylen~ Dichloride :sol ution.
Dissolve 0.1 g samp le in 100 mL Wate r.
Di s ~o l v\.' 0.1 g sample in 100 mL Isopropanol.

3.0 I dcn tifi ell t jon:

u) By IR
The lR spectrum of the Sll nlple should b¢ concordant with the lR spe ctrum o(the
referenc e/ wo rk ing srundard .
.\pr\Y I-~ drops of Linagliptin working slUndard 10 KBr cdh. anli rtt:ord the infrared sp~\,;' Lr;j
bt'lWccn 4000 em' l and 400 em'1 taking Kill' as refere nce,
• S~lmple prepara tiun:
,\pply \-2 drops orlese sample La KBr cells and record the Infrared spectra bell. . etn 400U cnf '
:tnd -100 em' l lak ing KBr as reference.
Contpare tht infrared spec.rra of Ihe t~st sample with thaI of lh~ workin~ slJ l1dllrJ.
• Specificat ion: The infra red spectrum of Lest sample sh ould ma lch with t hill of the Lin ag, llpl in
w(,rki ng standard
b) By HPLC:
In t)SS;) y lest. the retcnt tun time of prillcipal p (,~lk oj" s<lInpJe prtp,\l'(jl iOI1 ",hou ld c orre spon d~ III
princi p,tI peak ()bservcd in stlll1dard preparatio n.

4.0 los s on Drying;

lJI;cigil a glass -s toppered . shallmv v.. ·eighing bOll k thm has been drie d at 105°(, for 30 l11il\1.II<;; "
(W I). We igh accuratdy 1g of the sample in {he bottl e replace (he Cover. and acc ur'Ht' I~ \\t:iph
(IK· bollil' and the cont,,4tlts (W~), By gentle. sid ~ \\ be shaking, clislriblllt' {hI;' les\ spl'Ci n' l'n ,l~

-'---'­
evenly <IS prl:lcti.::nblt' to a depth of abou! 5 1111ll , Place the loadt'd bolt\<;; In lhe drying chulIlbl. " i".
r..::movmg the SlOPPl't' and leaving il ,ll so in lhe chamber. Dry at 10 5" C for 3 hllUl '~. l.' pull

f---. ; N" m, - -1
~ ig n.~IU f'e - ..- -
Pr cp:l r ed By
Abhi::ihl'k Sa\lji yani
A bh ~.h!!4
l~
t~·,-

.
C hecked By
Jig i ~h(j Veer ..

*~
. -
=r I
Approved Br
·· -'-Chl'~':l!~ p l"( lj ;;;;·l i· ·
-­
"'<II
~ D atI..' I ".1 11" ln l l 061 10 IQO'l.'L -"'C6Ti·tw L

~i~:~~~~:
 4.
-:"II.
QUALITY CONTROL DEPARTMENT
Shankus
Pharma Pvt. Lcd.

STANDARD TEST PROCED URE

Product Linagiiplin
Department QC STP No. LOPISTPIOOI IOJ
Supersedes LOP/ST P/001 /02 Prepa red on 0611012022
Method Reference In~H o u $e Effective Date 11 11012022

opening (he chamber, close the bottle promptly, and allow it 10 come fO room temperalure in
desi ccators before weighing (W3).
Calculation:
Calculate Joss on drying, in %, of the sampl e using following equation:
% Loss Oil drying 0:= (\V2·W3l X tOO
(W2-W I)
Where,
WI ""Weight of glass·Slo ppard bottle (g)
W2 =Weight of gla55-Stoppa rd bottle with sample before drying (g)
W3 =Wcighl of glass- Stoppard bottJ e with sample :ifter drying (g)
5.0 Sulphated Ash:

- .
h!nilC the silica crucible in a muffle furna ce at 600±50°C for 30 minutes, cool the crucible in a
desiccator and wei gh it accurately (W I)' Accurately weigh and transfe r about 19 of sample into
the c nlci ble (W 2). Moisten the sample with Im L of sul phuric acid and heat gently on a hot
plate at a low temperature until the sample is thoroughly charred. Cool and moisten the residue
with I mL of sulph uric acid and continue heating gently W1til the white fume s are no longer
evolved. Ign ite th e s(lmple in marne furnace at 600 ± 50°C until the residue is comp letel y
incinermed. Ensure thai fl ames are not produced at any time during the procedure. Coo l the
crucible in a desiccator, weigh it and note down (W 3).
Cal culate the residue on ignition of sample using followi og eql1ation:

Res id ue on ignition (% w/w) W3 - Wl x 100

W2 W t
If the amount of tile residue so obtained exceeds the limit specified, then repeat (he moiste ning
wi lh sul phuric acid, hea ti ng and igniting as before us ing II 30 minute igniti on period until two
consecuti ve weighing of the residue do not differ by mOre than 0.5 mg or until the percentage
of residue compli es with the limit. Conduct the ignition in a well~vent i tated hood but protected
from air cun'cnt s a nd at as Iowa iemperature as is poss ible 10 affect the complete combtlslion
of the cnrbon.

P repared Dy C hecked By Approved By

Name Abhi shek Sa vjiyani Jigisha Veer Chelan Praj apati

~~
Signatur e
Ah~iskll:.'" &
Dale
~ (, 11"11", 1 . -,I: :1.. OGllol 1.01~

/"g<'2 of 12
c..\1~L~ \\0 \{O< ~
 4.
~r
QUALITY CONTR O L DEPARTMENT
Shan'(us
Pharma Pvt. L(d.

ST
- AN DA
-- - - - -R-D TEST
- -- - -P ROCEDU
- - - - R- E
­-

Product Linagl ipti n

Dep artment QC STPNo. LGP/STP/OO1103
Sup ers ctlcs LGP/STP/001 /02 Prepared on 0611012022
Method Refer ence In-House E ffe ct ive Date 11 /1012022
- -- ­ - - -­ - - L..-_ - -­ - - - - - - -

6.0 Hea vy metals:

• Lead nitrate stock so lu tion prepa r ation :
Dissolve 159.8 mg of lead nitrate in to 100 mL of water to which I mL of nitric acid has
been already added , di lu te to 1000 mL with water. Prepare and store this solution in glass
Cll~ Ha i n e r free fro m soluble lead .
• Standard lead solulion:
On lhe day of use, dilute 10 mL of lead nitrate stock solution to 100 mL with water. Eacb mL
of standard lead solution contains the equivalent of I Opg of lead. A comparison solution
prepared on the basis of 100 mL of standard lead solution ~ s per g of substance bc:ing tested
contains the equi va lent of 1 part of lead per million parts of substance beingtesled.
• pH 3.5 acet ate buffer:
Dissol ve 25 g of ammon ium acetate in 2S mf.. of water, add 38 mL of G N hydrochloric
acid. Adjust, if necessary, wi th 6N ammonium hydroxide or 6N hydrochloric acid (0 a
pH on .5. Di ssolve and di lute ( 0 100 mL with wa ter.
• T hi oaccta mid e TS:
Di s~ olve 4 g of tbioacd ami de in 100 mL of water

• Glycerine Base TS:

To 200 g of gl ycerine add water to bri ng the tolal weight to 23 5 g. Add , 140mL of 1Nsodiuru
hydroxide and 50 mL of water.
• T hioaceta rni dc G lycer ine bas e T S;
Mix 0.2 mL Thioacetamide TS and I mL Glycerine Base TS and heat in a boiling water
balh for 20 seconds. Use the mixture immedialely.

• Sta nd ard soluti on prepar ati on :

Into a co lor comparison lube, pipette out 2 mL of standard lead solution (20 ppm of
lead) and dil ute WiOl water to 25 mL Adjust pH 3.0 to 4.0 by using I N acetic acid or 6N
ammonium hydroxide. Dil ute to 40 mL with Water and miX" well
• Sampl e p repa nll ion :
Weigh about 2 g of sample in a silica crucible, add sufficient sulphuric acid to wet the
Prepared By C hecke d By Approv ed By
Name Abhishek Savj iyani Jigi sha Veer Chetan PrajJpati
Sign:H ure A>\J5~ .;1}i!$W£..­ $
Dal e
t1ilJ1l. h n1 1 ~£1101Qo ')7 OGI I _11-< n.­
--

G1~l
, n3Ir~<
 ~.
-:p-
QUALITY CONTROL DEPARTMENT
Shankus
Pha rm;t Pvc. Lcd.

STANDARD
- - - - --- - - T
- EST
-- PROCEDU RE
--- -

Product Llnagliptin .
Departme nt QC STP No. LGP/STP/OOI/OJ
Supersedes LG P/STP/OO I/02 Prepa red on 0611012022
Method Reference In·House Effective Date 11 /10/2022

sample, ignite the sarnple carefully at low temperature until thoroughly charred. Add to
lhe charred l1la~ 2 OlL of nitric acid and 5 drops of sulphuri c acid and heal cautiouslyuJltil
white fumes are no longer evo lved. Ignite preferably in a muffle fum ace, at 500°C to 600°C
untillbe carbon is completely bum off. Cool, add 4 mL of hydrochloric ac id. Cover digest on a
water bath for IS minutes, and slo wly evaporate to dryness on a waterbath for 15 minutes.
Mo isten the residue with I drop of hydrochloric acid, add J0 mL oThol water and digest for 2
minutes. Add ammonia solution drop wi se unt il the solution isjust alk2lline to Litmus paper,
dilute to 25 mL wi th wa ler and adjusl pH between 3.0 to 4.0w ilh djlute acetic acid. fi lter, if
necessary, rinse the cnJcible and filter with 10 nll.. ofwater. combine the filtrat e in a 50
mlco lor comparison tube, dilute (0 water to about 40mL and mi x.

• Pro cedure:
To each of solution containing sta ndard solution and sample so luti on, add 2 mL of pH3.5
acetate buffer, then add, 1.2 mL o f thioacetamide-gi yccrine base test solution, di lutewilh water
to 50 mL, mix allow to stand for 2 minutes, and view downward over a while
surface. Co lor of the so lution of test preparation should not be darker than that ofstandard
so lution

7.0 H. elated Substa nces Dr I-IP LC;

• Prepa rati on of Buffer solution :
Weight accurately about 2.72 g of potassi um di hydrogen orthophosphate (KH 2P04),
Irnnsfer into a beaker and add 1000 mL of ill i.Q wmer. Adjus t pH .3.5±O.05 with
Orthophosphoric acid.

• Preparation ofMobilt phase A:

Take 900 mL of buffer soluti on and 100 mL of methanol, tra nsfer into a beaker. Degnsthe
mixture and fiher lhrough 0.45).t membrane filter.
• Prt'paration of mobile phase B:
Take 700 mL of acetonilril e, 150 mL of methano l, 150 mL of mili-Q water, Transferi nto a
beaker. Degas th e mixture and filter Ilu"Ough 0.45 ~ membrane filter
• P reparation of diluent :

Prepared By C becked By Approved U)

N:un e Abhi shck Savjiyani
I
Ji gisha Veer Chelan Pmjapali
Signa ture Abki;U!S.. ~L{) ~ ~
Dale ~,.II ;t1m)] . ;-,d,,/o_" 1. 06/IO(l.-0,", -
~~e4ofI2

G1~i\O\H'-< ~
 QUALITY CONTROL DEPARTMENT
••
"!'J.
Sh.lnkus
Pharmil Pvt. L[d.

STANDARD TEST PROCEDURE

Product Linagliptin
Dcpal-tmcnt QC STP No. LGP/STP/OO lIO ]
Supersedes LGP/STP/00 J/02 Prepared on 06110n022
Method Reference In-House Effective Date J JII 0/2022
---­

Mobile phase-S as dil\Jent.

• Preparation of Standard solution:
Weigh and transfer accurately about 20 mg of Li nagliptin reference/working standardinto 100
mL volumetric tlask. Di ssolve and dilute to vo lume with diluent.
• Prepar-ation of sample solution:
Weigh and transfer at.:curately about 20 mg of sampl e and transfer into 100mL
volumetricila sk. Dissolve and dilute to volume with diluent.

• Chromatographic cond itions :

C olumn Inertsi l ODS (250x4.6)mm, 5.0).1 m or equivalent
Column oven temperature 45 °C
Flow rate 1.0 mVmin
Inicction volume 10.0 uL
Wave length 225nm
Run Time 60rnin

• Gradient programme:

Time Mobile phase -A('/~ Mob ile phase -B (%1

I­
0.0 75 25
8.0 75 25
30 45 55
40 25 75
50 25 75
52 75 25
60 75 25

P repared By
, ,
Checked By Approved By
Name Abhishek Savjiyan i Jigisha Veer Chetan Prajapati
SigRlltUI'C /JblJsW6. ;to ,o~ §"i),
Date , [ ll nIJ mlL o61!0pO......
...ohillJ2.02.2.

P':1.ge 5 of 12

.:W'~-n \0 \-i.N ~
 ~.
~.
QUALITY CONTROL DEPARTMENT
Sha nkus
Ph.mna Pvc. Lcd.

STANDARD TEST PROCEDURE

Product Linagl iptin
Department QC STP No. LOPISTPIOOII03
Supersedes LOPISTPIOO 1102 Prepared on 0611012022
Method Reference In-House E ffective Date 11 / 1012022

• rnjectioD seq uen ce:

S. No. Description Number of ill iecti ons

I Blank I
2 Standard sol ution I
3 Sample sohltion I
4 Standard solution BKT I
• HPLC Analysis;
Equilibrate the HPLC system and colwnn until a steady baseline is obtained.
Proceed as pe r injection seque nce.
Linagliptin RT about 14.6
• Accep tance crilcrin :Iud sys tem su itability:
Tailing facto,.: The tailing faclor of Llgaglipti n peak in standard solution shou ld be
less than 2.0
Theoretical plales: The theoretical plales of Linagli ptin peak in standard soluti on
should be mOre than 2000.

• C alculation rind result reporting:

Examine the blank c hro marogram for any ex(faneous peaks and d isregard rhe cOiresponding
peaks, ob served in the chromatogram of sample sol ut ion. Report theres ults as per area
nomlalization method.

• Column washing: After (he completion of injec tion sequence,wash the column with a
so luti on afwater and methanol (50 :50) at least for one hour.
8.0 Assay By HI'LC:
• Prc p ~ration of mObile phase -A:
Pipette out 0. 1 mL of Tri-fl uoroacetic acid, transfer into a beaker, add 1000 mL o fMi!l i Q
water. Degas the mixture and tilter through 0.45 !l membrane filter.
• Preparation of mobile phase-B:
Pipette out 0.1 mL o f Tri- flu oroacet ic aci d, transfer into a beaker; add 1000 mL of AceturulIiJ e
degas the m ixture and fi lter rhrough O.4SIl membrane fi lter.

Pr epared By Checked By Approved By

Na me Abhishek Savjiyani l ig isha Veer Chetan Prnj apati
Signature
.AhJ.~ ,·ullo1I).f.._,. ~
Da te
...n.G..fl,f I ~ J 1. o6/ l ol?Ml_ ""J.l, ol>.o1,--

~G 110 klJ.1 i
~c 6ofl2
 Q UALITY CONTROL DEPARTMENT
••
-:, ­
Shankus
Pbarma Pvc . Lid.

STAND AR D TEST PROC EDURE

Product Linagliptin .
Ucpartment QC STP No. LGPISTPI001103
Supersed es LGPISTPIOO 1102 Prepared on 0611012022
Method Referen ce In-House Effective Date 1111 012022

• Prcpar:ltion of diluent :
Degas the mixture of 250 mL of Mobile phase-A and 250 mL of Mobi le phose-B. Filter
thro ugh 0.45 pm mem brane filter.
• Prcpa l'a tion of sta nd ll l'd so lution :
Weigh accurately about 50 mg of Linagliptin \vorking standard, transfer inlo SO mL
volumetric fl ask, dissolve and dilute to volume with di luent. Transfer I mL of the
SolUlion to 10 mL volumetric fla sk and di lute to volume w ilh diluent.
• Preparation of sampl e solution:
Weigh accurate ly about 50 mg of sample, transfe r into 50 mL vol umetric fl ask, di ssolve
and dilute to volwne with diluent. Transfer I mL of the solution to 10 mL volumetric
fl ask and dilute (0 volume with diluent.
• Chromatographic conuition:
Column [nerlSi! ODS ([ 50x 4 . (i}mm , 5 ~ or equi valent
Co lu mn oven temperature 45 D C
Flow rate 1.2 ml/min
I n_iection voluUlc 10.0 uL
Wave Icne.th 225 nm
Run timc 20 min
• Gloadicnt prograDlme'
Ti me(miu) Mo bil~h a sc -A-.to/?l M obile J)h ~t s e -B (%)
0.01 95 5
3.0 95 5
10 5 95
15 5 95
17 95 5
20 95 5

Prep:tred By Ch ecked By Approved By

Na me Abhishek Savjiyani ligisha Vee­ r Chelan Prajapati

~
Signature Ab h~ ~
Date na Ilnll . ) 1. oGIlo('l.C' ~
chil i'll (If) ? 1

~~~I~~~-i
 ~.

QUALITY CONTROl> DEPARTMENT

-:"11­
Shan 'ms
Pharma Pvt. Lcd.

STAN DARD T E ST PR O CEDURE

Product Linagli ptin
Department QC ST., No. LGP/STP/OO1/03
Supenedes LGP/STP/001 /02 Prepared on 061 10/2022
Method Reference In·House Effective Date 11 1I 0n022

• Sequence:
S.No. Descr:iption Nu m ber of i!ljections I
I Blank I I
2 Standard solution 5
3 Sample solution 2
4 Standard Breketing I !

• HPLC Analysis:
Equ ilibrate the HPLC system and col wno until a steady baseli ne is obtained
After the sys tem has bee n equilibrated, inject diluent as blank , standard SolUlion.
Ensure that the system suitability parameter meet the accepl ance criu:ria.
Proceed as per injection sequence.
• Accep tance criteri:l an d system suitability :
Relati ve standard dev iation: The %RSD should not be more than 2.0% for fi ve replicate
inj ections of Standard solu tion.
Tailing factor: The tailing factor of Linagli pti n peak in standard so lution shou ld be
less than 2.0
Theoret ical pl ates: The theoretica l pl ates of LinagJiptin peak in standard solution
should be more tb :tn 2000.

• Ca lclIhHion an d. r esults:
Calculate the assay on dry basis for sample using the foll owing fo rmula:

- ASrL CS'ID X P x 100

%A,say (O DB) - - A Xc (I OO. LOD)
STO Si'l
Where,
ODS is on dry basis
ASPI..is the average area of Linag liptin peak in the chromatogram obtained with sample
preparation.
ASTD.is the average area of LinagJiptin peak in the chromatogram obtained with st andard
preparation.
CSTD. is the Concentnltion ofLinagliptin reference I working standard .

Preparcl1 By Ch ecked By Approved By

Na me Abhi shek Savjiyani Jigisha Veer Chelan Prnjapati

~
Signa tu re
AbJJJ/Jt.... ~
Date ~r. r L11 loll , I . I~ o ' '" ~V<>I··).4.
~C 80f1 2
C\'1 1fb\ \0 \«).(~
 QUAL1TY CONTROL DEPARTMENT -••­
Shanku$
.,1
Plr..l rmd Pvt. Ltd.

STANDARD TEST PROCE DURE

Vrod uct Linagl iptin
Dt:p:1rtmcllt QC STPNo. LGPISTPIOO 1103
Supersedes LGPISTPIOO 1102 Prepared on 0611012022
Met hod Reference In-House Eff«:t ive Date 1111012022

CSI'l. is the Concentration of Linagliptin sample.

P, is (he potency of Linagliptin reference/working standard.
LOD is Loss on drying oflhe samp le.
• Co lumn w;lshing:
After the completion of inj ection sequence wash the column with a solution of water
and acetonitrile (50:50) at least for one hour.
9.0 Enantiomeric Purity (By HPL C)
• Dilu ent ffllank: Mobile phase

• Mobile Phase: Ethanol: Die(hylami.ne ( 100:0 .1 v/v )

• Chromatograp hi c Conditio n:
Column Chiralpak AD (2 50x 4.6)mm, 3.0~ m or equivalent
Wavelength 295 nm .
Fl ow rate 0.5 mi l minute
Tempe rature 25 ' C
Injec tion volu me 10 fll
E lu tion Isocratic
R un time 30 min
• S·lso mer Impurity stock so lution :
Weigh and transfer 10 mg of s-jsom..: r impurity in to a 100 mL volumetric fl ask, ndd about 50
mL of di luenl and sonicate to dissolve, make up to the mark with diluent. m ix well and
sonicale.
• System sui tabili ty Test (SST):
We igh and trans fer 20 Illg o f stand ard in to a 10 mL vo lumetric tlask, add about 5 ml of
di luent and soni cate to dissolve and OJ ml ofS· isom t:r imp urity stock so lution make up to
the mark w ith diluent, mix well and soni cate.
• Test SO lution:
Weigh and transfer 20 mg of test sample in to a 10 ml volum etric fla sk, add about 5 mL of
dih.1em and sonicate to disso lve, make up to the mark with diluent , mix well and SOruC<l le .
• S:ystcm Suita bility:
Resolution between isomer (Imp A or S isomer) & Linagliptin should. not be less than 1.50.

Prepared By Checked By Approved By

Name I Abhishe k Savj iyani ljgisha Veer Chelan Praj apat i
Signature ,jhh/;~ ~1u.e.-- ~
Date ~dlo j, 1\1 1 {; I Jai 9 0'??
or'",,,­
<!><l\ \

~\~i~~I~
 ~.
':1 -
QUALITY CONTROL DEPARTMENT
Shanl(U5
Pharma Pvt. Lcd.

STANDARD T EST PROCEDURE

Product Linagliptin
Depart ment QC STP No. LGP/ST P/OOII03

Supersedes LGP/STP/OO I 102 Prepared on 0611 012022

Method Refen:nce In· House Effective Date 1111 012022

lnj ect 10 III of the blank, system suitabi lity so lution & test solution, record the
ch.romatograms & measure the responses for the peaks ofLinagliptin & its isom er. Calcultlti.!
the result by area normalization method. Di sregard peak due to blank.
Formula:
% of S-i somer [Imp Al = Area of Imp A or S isomer fro m the test solution x 100
SUlll of the total area obtai ned from the test solution

10.0 R es idual solvent by CC

• Preparation of blank:
Transfer 1 mL of Dimethyl Sulphoxideinto a vial seal with a seplWll and cri mp cap.

• Preparation of standard solution:

Weigh accurately about500 mg of isoprop)::i nlcohol , 60mg of dichloromeUlanc, 41 tng of
Acetonitrile, 500 mg of Ethyl acetate and 300 Methano l in lOOml of volumetric fl ask
conta ining 30-40mL of Dimethyl Sulphoxide and make up volume with Dimethyl Sulphoxide
and mix .
Transfer 5mL of this solution in to 50 mL of volumetric flask and dilute to the volume with
Dim ethyl Sulphoxidc. Transfer I mL of thi s sol ution in to a vial seal with a septum ,lOd crimp
cap. (S ix via ls)
• Prcparntion of sa mple:
Weigh and tnUls fer accurately nbout 100 mg of the sample to a vial , add J mL of Dimethyl
Sulphoxide, dissolve, seal with a septum and crimp cap.
• Gas chromatographic conditions:

• Colomn D8·624. 10-0.53 nun, lerurth·30 meter, 3.0 ~m or eou ivulent

Detect or FlO
Catrier gas Nitrol.!cn
Detector teml)eraturc 250' C
Split ra tio 50:1
Hvd rol!cn flow 30 mUmin
Airflow 400 mUmin
Mullc up flo w 25 mUmin

P repared By Chec ked By App roved By

Na me Abhishek Savjiyani Jigisha Veer Chelan Prajapali
Signature AiJ, ,'Jb!f.~ ;;JAufjiv.j;.-. ~
Date O ( :{ lor 1.0\4.­
" r. lin 10.11 ad ,, /o",,·, .

).'.:;e10 of 12
q:.uttl,0 \~O <"'
 ~.
-:'II .
QUALITY CONTROL DEPARTMENT
Shankus
Ph''1rma Pvc. Lcd.

STANDARD TEST PROCED URE

r::--o
Product Linaglipti n
Departm ent QC STP No. LGP/STP/OOI/03
Supersedes LG P/STP/OOI102 Prepa red on 06110/2022
Method Reference In- House Effective Date 1111012022

Column flow 3.0 mUmin

Septum purge
3 .0 mUmin
now
Ruo lime 33 min
Ramp eC/mill) Temp. (0C) Hold (min)
Oven
temp. Programme
. 40 10
10 220 5

• H ead s pace conditions:

Eauilibration time ] 5.0 min
Pressurization time 0.20 min
L oo!} fill tim e 0.20 m in
L oop eq uili bration time 0. 05 min
Iniec t t ime 1.00
Maximum G C cycle 40 minutes
Oven temDera ture 90°C
Loon temnerature
-
100°C
Tra nsfer lin c temperature 110°C - -
• Procedure:
Injecl blank followed by six replicate injections of standa rd solution and then blank in single.
Record th e chrom atogram and ca lculate the system sui tability parameters . Li mits are as below:
• Relative standard d eviati on: Relali ve standard deviation of area of si x replica te stand ard
injections shoul d not be more than 15.0%.
[f sys tem suitability passes then inject the sample preparation in duplicate and record the
cllfomatograms.
• Calculation: Concentration of each solvent can be calculated by the fo rmul a as below:

AO" L x-·,-x
Solvent (ppm)= --...:!....- P x 10 ~
W- rn - I x - 5 x -
Asm WSPl 100 50 100

P repared By Chec ked Dy Approved Ily

1--­
Name Abhishek Savjiyani Jigisha Veer Chetan Prajapal i
Sign ature Abh/;,JJif.. ::JJ"oJ,; v ~
Date
-".Lllci1uH 'l rd, OI9n?? D611. \1.< "'-­
-
Pit'" I I of 12
@66T\o \.I.a~ \
 QUALITY CONTROL DEPARTMENT ~-
••
Sh ankllls
Ph.1(nta Pvt, Lcd.

STANDAR D TEST PROCEDUI\E

Produ ct Lina gliptin
Department QC STP No. LGPISTPIOO1103
Supersedes LGPISTPIOO1f02 Prepar ed on 06/1012022
Method Reference rn ~ House Effecl ive Date 11/1012022

Where,
the area of SPL.
ASPL,i :;
ASTD,is the average area of STD.
\VsTD,is the weight of STD.
Ws PLis the average weight orS PL

11.0 Abbreviations:
STP : Standard lest procedure
QC : Quality Co ntrol
No. : Number
AR : AnaJytical reagent
°C : Degree centigrade
MP : Mobile phase
~IL : M icro litre
mm : Millimerer
!TI L : Mi lliliter
g : Gram
mg : Milligram
L : Liter
PPE : Personal protecti ve equipment
min : Mi nute

Prepared By Checked By Approved Dy

Name Abhisbek Savji yani Jigisha Veer Chetan Prajapati
Signature
Da te
Aj,/J.> UA..,
~ 4
-061
..Jlcj ln 11~ I L Oe !. ·1. ' .­ ,· /'1.< '"'-.
. ~ 12 0fl 2

~tG\ 'o\<D.z\
 ASIAN JOURNAL OF PHARMACEUTICAL AND CLINICAL RESEARCH ~/~r~ Onlllle·24 SS- mJ
Vol IS. Issu e 8 , 2022 \l Nnl - Q47..21-t1
RCh'arc h \rl!ck

DEVELOPMENT AND VALIDATION Of DISSOLUTION METHO D FOR LlNAGLIPTIN l)\BLETS

MEGUI\Nfi PANSARE. MR INALINI DAM LE*

Ilo: panm e nt o f Qu:tlity A)sur.oncc:, AUlnd l:a Sh n Sh lv..,1Mt' !I1 o na t Soci<:t)~~ ( <llIc lle o fPh:ormacy. Ke nne d y Rn,ul . Nu r RTO Pune,
MlIh..a r.n hln. Indl • . Email: d;lI nle .m c~.. in llu~op.cu m
R~ell'H' 09 MOY 2012, RMud andAcUplw: 20 JU II" 2 02!

ABSTRACT

Oblective ' Lm.,IJI'OIl i~ lIlII,1 '0 Ir.,:aIIVI"',2 d,.•hclc'" It i '"' ,llbl1lo: ~mgly.s'" JI\i! billc! SlncC' Ihl're I.' no NIi~ul d l$~"I"fl"n r,~~t" n h"I,.)
1'1urm.\C0fK'1~. 111" ,'(, 1s,1 n.W HI d~.. "'p
~ ",elhod I"r I~lllri d,..""h.lII"" III llnJ.&1'j'>lln 'mml',hal(' lele• ...e •.>ble,

Me tho ds: h,r ~".Ibl Ihm): ,hnulUlwn mftll.....t. V3rKIlL\ mi!'d, .. vollLmt 0( m...Jia. _.nd .))t"t"J uf rotation wen- ITIL'\!. Qu3n1,fj,.lIIOn ,/ ,,,>.•
u~ ul.on
$~mpl~s WOl." corrtrd ....., ll~"'g HPTLC ~nd UV I~'·'hnd. TU_I~~le p~~lhlttd ... "h ,do I':ci 10 (1 F ..~ w.~ u$cd n .1.l1'"n....}' ph~~\· ~I"I m"I"lf I'~ I,,)
""Jl"l"t"'d fill (1\<1 d ....·~.lIpnll·'" I'fTu.: pl.l1t1 _~ mc'hannl: toluUI" In '" "'IiI nf 7:3 , / •. 'the n""hde p ~sc ... ~ , ~1I11Wl-,,1 fillran' J di,t.III' ,. nl 70 "~m
.. '.~ S,l{l..,-"uon (On,e Sl'I WH 20 ".hl_ Ol'tecrlon ....1\'tI~n~lh ~"tlN~, 294 "m.

R",. ,,'U, Th... "",~t ,ult.lLle ,;lInd.t, ... n fllr d, ,"olu t l" " <)fI"t.\ithpllfll_.hl~1 "," h'u nd ", b., d"""I!llIul1 .11'1"'1'311" ty»l' II (p."ldl ...) ,,~'"~ 9(11111\1 O.! Nih I
.," n"'d,um dl Sl'~<'d {lf7S tl'IO The ophmm'u {hro!tt~U>RnphlC cond,tlOn ~~uh .. d til ("l1m/,:ocI lund "I Rf valt>C o r 0,761U.02

Co nclu sIo n: Bolh 'ht c l"-om~r~~r~l'hl(~n.! ' Pffit'O$Ct'I.i( n,e(hnds ...·ltiJ:h w~re 1J5 wd lor qo~nllfi(~tiorl W"'l'e foond to 1>f. lineJr ""th I" "~h'" ,,10.'i'l2'l
,,,.I U.'l'll B. r$.'peo:-tl"dy. aUHrJIC. precis .... ;1 nd nlbu",
I\ey.,.o nh : HPTl.£.. UV WCCtrt'l~hllt(II"eUY DIWllulmll Mct~ od ~~Vl'lnpmCnl, \'ahd~! , on Llnaglir" n.

lJ 20HTIt~ AUlhors, p"ltlhhl.... lly Inn(lVMt< A,-a'I~mlcs..lf"~l's Pvt [.I(t. TIlls Isanopen '" ctsSartld. "nder th e [1.: llY !iet-IISt (httr / iW"~IJ""Ulnnn""",,]'~/
II,'f':I$P'/br!·u 11IJOI hnp !,I,lul",oTIt/11122 I "'~/~tpcr2022\' 151fi.45 14_~. routnJJ ho'n ~IMg" http-s'lItnn"'·Jre,l..u!~ mL(s.Jn!I<' .. m~J~/jn.k"f'hp/"Jl1<T

III; TROOUcr .ON MlIHO OS

I ,,jI\I;I'I;n \. ~M'd til I h.. ~~(~\~ II\ 01 nOIl·I'.~ulln-de1'M'ndl'l1t Instru men ts
,hJh~ I ~S m.-il,nts I( ,~ . nll'nl bt r (If ((.11,., "g!tpttns wlt'llt ~re o...-Iv D.ss.n'o·.l(In sa"'pt~~ w ('te .rul.. ~ed U"~R (""'~R II"I!!: <y'I~I~
~nl~ O!'P-i mhlh'lnn th~l MI.' IhPl.'plidyl prphdl.~'" ,nh,I"lnl" tIl. {IW.c.\n; 1.4.2),md ShlmJdru UV 17110 UV-V'S!I'/.(: ,V",-n<'ph .. I'>lIlelt·r,
IJ~~ItI'lltJn dtN1>iuUy t< 8 (.1M)- ~-.mHn('tp'~nd'n·I·~il·7-1l"I'l'vny\ t"I';'" ~nd other I.'\Illtpml'llt u,cd ..-en ~ 1\UnlidJu "''' 120 An,'I)'I'" ,\
:I mcrhyll -1I4ml.'lhvlqumJlohn-2·,1l m~th~'il l'''fi,,~·2,6dJ()M {21 BaiJ.n·.,.lap;l!1 El«trnla l'l 01 Dill Dlssolull un dPP,"-JIII1 UW (III'" III
h , .".,IIo""$h III wlt'l" so/,d \ubst.1('1o., ",hirh "vfry '['illI/V iolub\, ~nll \...1lJtronlu t:r I I !lUll) DIJILuI pI! mctn
'" ....Ier i<o)prop.\]11I1. .J<.t'lOtl(' fo(Ilubll': In nltll'l.ln_'1. and .;p.uing!j'
wlubl~ 1I1/:tlhanol Sfrw;«tt.l lt} it 1$ (~Ig,. I); fhe rf'< IImn1enll •.,J do,.. Ch t'mlcats ~nd reaJ:e o l5
1""ltn~tI'plln f~ 5 mg onnl d~.ll'll. h lS ... "~,I~blr.1l~ I.\hle. d •• ",!!/, fnom Lln.lglplm rPI.. ft'nc~ ,I~nd."d \Vi\ nI1l&u, ..,1 U g,1t r ;u' _.. TI>.
,,"I! .... bf-I d.nm of 5 mIt per (.lblel. <hem,· ~I, u~~d wert' I1lMJ""I .."d "'dler N 1I1'U.ltr~d ... o" oJ lulu,·'11.' "r
AR Kr ,d~ M~t1"'nol ...'~s ptn>,;h3S~'" f....' m \I",~~ I.Jf~". ,~.,,'C~. Pvl L:o.L
1t,c ItC~l wily of asSC!<"nR IlIcrlxul j( I.'O'CXY ot drul t< 1'1 ,·tt'o MumlMI. lnd.... ~nd tOlu tne w;t~ purmnl'tllrum UlbJ thm'" I'vt l~,L
,k:Ilrm;"••tH)f1 0( h ,\~,,~i!3blloty wh.~h" ,tonI' whe!! n n~", /urmulaW"n M"m',u In.!'J For dl " "ll1tion PUIll'O~" m"rk("j!ld I~"I .." "fb~ .. ' rl~nn
I' Inlnx!lKed fllIlI m.. rkct HOt\~I'I, Iii mon,l.., b.llc/I I" bat(h 5 n'Il """,... PU(,h.i.ed fW>m 1oc~ 1 ph~rm:>C}'
(I)"~"tency. thIS m.. ,hoo.ll.oecoml"l costly, \t'd~,u,. al><lllm~ nlt"umlng.
~ ~ n,c. lit "Ir,u dJs'oOlulliIr: t.", ""\!'t~ttl ,1' 114'1' qu,Uy r(lmrnl tnul
to qu.nu.. I'v~l) h~lue ')bullt bl(>logtcdl .. ,,_,I.bd,ty ul d"UK (",,'m
I'hu~I' • lie bunt', of pH 45, <"IU ~ tt'
p"'parc'd lreshly ~~ jX" Ir 18t
buff~r of pI! 1, an.! 0,1 'OJ li e "'('c.'

II~ tnnnu\;" "'f1 f~ j, In \'Urn 1C~1 " ",dill In jluid,nl: £tJrmlll.ltl,'n 4~tl
(kv~lo p me "t, moonor m.nur~Clul1t1lJ ~tnCNS. ~5Scssln~ q ,,~lily of Ch romal OlCl'ap ll ic f o n d ltl o ns
hal.-ll. • nJ mal bt IIW/I,I til pre,.h,! '" v;vtJ ;>t!rfr"",~n,~ Itl I..rms nf The Gu:rnllhC:lllun 01 d ':"so("lion $3mpl~s ....,,~ pnlon n<'tl <Ill \I,.,,; l'l.t
h,oJvJl1allility. DI.IS<lI ,,\ion Ie'st 1$ JI~(I II'l'll (0 Identify hllllv.JI.hHl ly pbt~ 1'''''' lJi\l.o:\t with ~ IIitJ "eI 60 F,.. , S.lm~l", w.. r.· _IPP~t'\J Oil jll.lt~
f:'ruhl~l'!ts ,~ !t d to a~~,;., th .. n~Nl for (unh.., III000qulV'.. l~nce rUt) 'Uldi~. III lhc fo rm of (0 ,,,, n h;m.! l.I",n~ LOO t, 1 "'IIIpl ' ~yl "'~~ ,,'til lite l"'lf' .r
)d" t Lve 10 ,~ .. II.'-llp Jnd ~"~t·aj1p({l.allh.n~c\ (SUPAC) 151­ "'''tlll''tOmall< Li,w"'''1 ~jl"Il'~\Or IV 211 - 10 \",on \toILKi' dW1'Ib.,r .....-;t. ""'d

Th, Itltra rur!' 'U"i~r fo"'·eal.-.l .~~t IIl~)'t I. one PJJ'H't oj d!'<\t,hlt,on
".cth"" of j , n~id, pttn lI< tIlK HP LL and tlV If,]. To th~ lIrs: ot our
k"n",l ~dl('" ,h.. '1! ,~ nO rff\nrt of Ih~<uI"lInn "\~Ihnd n! h".Ighp''''
' ''!II$: HI'Tt.c ,mol UV ~m,'JI'1'OtL K{'l.'pln~ h. n.i"d . ltigh-lhmug!lpol
...!vam.lj:t of HI'TI.C. II Wb ~un."t~,...d ... urlhwh,k '" dt"'l'~lup
IIPTLt. Illt'tW f"t q ..,ln. lfinlinn "I lLn.lgllpltn In dl~ ... tul"·n II.'"l
" -<
'V',~r-
cy AJ. >--'Q
/. N
o
o

N N
.".­

f~ ,lzowoitJped 1lll'lhlKl w;•• VKhd3lt.'Cl a. j)l.'f hllt'rtLlI",n,,1 (ounnl

In' H~mtnn ll""110n IILIt) I':ujdcllllc~ (1) bolSCil 011 P JJ"n~I""" ~Udl~'
I '!H,
~p.....,fic.ty II"u"ry. pro,·,ulon. ~(\1I~f)'. JnJ ,<>b"'.n ..,, Pig. l ' Chefll iu l s trut lu ,. ufil n.1l".. ",i"
 1.1

I ' ~Ol rll~q/iiIlO<; p<ll~llyOJr l , % J" ' IlIJ"1 u,

a"w.. .10
r""~ J (I~~ <I II '1'\111"1 ~I\!~ ' r" ~ ~I\p'~ ~ " ! ) Il,l"v,Pq

')111.01 pupqfliu 0" J~lrY 'Jrwl"I.IM

• S1~u,,~oJl "III 91"-lJ$UOI.U"P I'lI41~ 1lI r~J! I.([(-"1' IV ,\)l'~"_"V

1 (fO!
~ ,"WI
1'\J~Il/:-'tl OS
pu rq/Su O~
lJ.n I Sf,(')3.i.l.d
'u,l ~t U ,!(Jilt! ,
[ AJIlI<l.uV

1<;\'0: il''''q/:lu 0.. IW; ~YO 1101(/<1 'pJU!WJJ1~p ~~h\ lllJpUI.1o.> " "I~\~Jlf;u ru~ j,I'lIllJ[d W" :>.\111)
pano!,!s lu nowv ON' unllrJ'I,WJ .)'1~ [,u/lh1 9 1 - ~ W.~, I "~ allu"J '!In JOI pur »olllillU JIJ..IIJ
JOJ P" " 'lI~u <;ll-~ ~ J" .)liu&l UI)II\', lUJ:)UO.l JO) 1",UlJUI .~d ~~." ,i1lJ'''''!1
.u 11l !ll1~ dIU OJ H11 !~ : I a l q ~~ U'
",!-I. -[l1 ~i!u ~ 'I ~ "~ U0!l nl0S H,ul' JI) ll!)<]r'lII,nun.' " I !~1I0IlJodnJd
;tSllods~ I''') Jl" l~~ 0, .\lIUqc S! ",mp~lOJd l e~!1AleUl' JO ,\IUrJu!1
AltII;Q''!'J

-- .-- .-_. "\Jud,jSl'I.Ill )OIII :'Wt'S I~ ~p,td Au~ ill:! IOU1l1' 101{l> ,\JJ'IJ. '~Idull::<' IIOIlI\I'''-'' 11 ru~
llnunlos p.ll'pUI'l~ \lOIl lllos oq,)JI'ld Wn,p.3tU UtJQnl''''''' P ~:Wi<1 ;"11 )lulX.{[,,1l?
,<Ij W~~S~" PU4l"'-U J" kl')~..,ooS -k l l\l ~, .... oJ ;j(j up 11->1'." Sl"""OOUKIJ

'VI
J.)!{lO JU :X>U;IS'-lJ~ UI Jll1j"ll ~ ~ l >;!;~''''1; \)1 ptJ lI1<'W Jrl Allllqr ~'11 " II
ifJ"ifrl~d~
_.
• "" UI13 PIT\l! HJ I Hd se SP lll sn qOJ
pur '.(Jl'.,")J~ 'UVI~P""~ '.(1\.1£3" 11 ',\luUJl3ds .e (p n ~ ~'l"latUl'II'!
mour_' QQ p"""q p'llep'J"" ~rNl !lO'n"'"
p"dol ~Aa p ~Aoqe ,lIll.

V -.
UOrlep tl l!,\ POI[J<IW

·p·'~A!"ue.u~ SUOllnJo~ p ~J"lm - un(J pilE P"J~II\I 'llO<i.

puc >.IJlI!J ~~·>l1l1l8nlJJ'l/ p'J,ll1!J Sl'Nll,u/il, . 5 UIJI\r:J/U.)'UOJ JO UI"'I'~UJ
''''
uU!lnl~~S!p U! U'lt!'llic u ll In UOllnIO~ \.>JepuPlS J 'iJ. 'lam. urW IC4 M
lJU" ""' 11'1 \lOr·11I \uTi ~"t"o '."Cl /ld " ul 510'0 'l ,H J IU<1 St·o ~'C lell1
.)I~~IP UI l,;uLlrrr~:':JP P" " Q'l i u!ld 'I~ ~uq 'S"t> Hd J~JJnq ~I"qllsoljrl
$''>I['.l lU;;J~U'p SU'$U ~>[N'l:'1 seM .(llllQIll'dIUOJ Jaw.:! -{til p"p~1" S!
pll~ '[ HII 1.)11"'1 ,:lJtlllJ T ) H N ' "0 a.J.)M PJIJ! ~ Ipaw , "O<lt., ~'U
uUI-l,'nW'3 ·...lU,)4 p , Ie 'In.>><> ~~\I.I.J"II!1.('I""Ul'l~4ns iIIn.Jp I" " " pILI' I~P\I
U(l!l:MI'''~'/Ji'W 'uopnt'" _'Id lll"r~ """'J P'1 11M l"~IJ 1~ 'J~l~'" 1';"'10«11)11" ~~O'U.>,' OJ "
110 lI.l a r ~s Ull IlJP u'OJ IWtl f11 0S511l UO!ICl ljUJO ",ooJlld ~ q~ "I,IU!J I~J!JiI " ul' lU I ~ 1'!UIlII~ ~W Ul I I dlIt'lll 01
.v1"i:..n.1U $1 I' 'r1Pill" ""'ln ltlSS!P ',"OJ) Uh\CJ p41' .... al8 S"l dlues 1.111\'
'(z ·::I'.i) lUll ~6l
t "I'qllvri:un.o JJII'd
'l'l>\ ~"'P'll~' II1~ v; I M r'" ~41 1'Jl ,~ ~, p·"pl,, ),,-, UIUlIIlU ~ LU ll O~i'-OUZ 10
.,~u~-' ... "'~ l.)M jhluur.w~e."lw/ lll1 S U Q11e.llU~." ")J I() uOllnlO)~ ~>OI>,)I./.I.
l(:tlfu "l iI,\~'" J O UOII» li <; ·p.:IU I "IE\\ 1111 006 r"r
I UIII(JSJo " um[O/I" 'I"' ~~ ~'/J~ Sl 1'111( U<;"".nJ
SlUI'Jw:ddr ,0 J.......t\ "4111",d""'l .<q p.)uI ~p" I>.ll uon"JO!>'!U ' P"PI "'I.v., U! 1
'W Ill P~tlI,~ JJ.lgM 1'~IIOj~!P
N l ' UP'u: S·~ l-ld 1"JJtl(1 J JE4u w qd 'E H tJ j~Utlq ~ \''-' I PW 4''1' r<p..>lU V "lm ',\
'IF" 1''>11\ \<.Ill SCM I ~al UOW 'I<lSS! P '~Jualj :HI"'" UI ~lqnIO' Iill'l~lrS U"'/lp~ ln IJD!I"ID.« IP JDIIv1l.>.)I"5
...... '" >1 u' 1<1I1l1CUI11~ql p;l\Jod., Sill ' S-~ lId J~lJnq ",e'ld,oljd pur '( lid
),}JJ"~ ~1l'-I\) 'lJ fJ N 1'0 "I " I c; nl<l~ '(I;>;)J,I iKj <>1 punVJ ,c."
untl'llltu'1 -~~r4d ~Il~nw sc (.\/A ~:LJ JU.l n iOl lOIl~III"ll\ liu ! ~,\ jJ.)lI,nqo
Al lll q n lvS .l~~"" '11"~.lj J~11,)8 '(A/ AS· ~) lo~e'!lalll _IUJQ1()JO IIIJ III p~".. .' j qv J)J,\\
~d .·qs >[p,>d J9dOJd ou pUt! (AI" S 5) J U""!,,1 ~l~~)~ I.('ll ~ II! I,~ ..... ~sqo
s.l.lns:ul i.r.lM ~~l'l'ld ON ·p"I.1J al"."" til{" ('L) ~<JanIOO -lou~1I1aU,' p ur -( AI.I ~;!;)
11J(' F41DU1 wAoJO,O\lIl 'l~/A 5S) ;I" ~1l 101 ;.lle1a:>E 1,(1I1~'~ 4)1\~ l a5t'lcl
'P~l/(I E "" \/;)41 pu c
~Jl4ou' ~()UIJP_' '.TIJ.dli .(q ;llllwrs UOIlI1I(\~~' P JU IIQII PJ!jl l u"nb JO"
q 7 1<11 'J,S J" a1llll'Ja.JIlI.}1 W Id"l\"-'''''' uonr.[{}~ ;>lcJ\I.I ~~ P"" IIQ""I""
I.J"l'urJ', .•111 ....lIlllp.'W UOll I110~SI P u, ,{J 'lIQrj5 uo!mlO' Jill ~U'OJ.lHI.lP D~ alo'lJ '~I"Jowlo /ln/~"'I<'S
IIl ll"/lIl> (W'ml"S
' II ilJ QlPnh IU ) t U! WU OOt-aOI
JO .1)lU~ ~OAO p<l\lue), ~~A\ lIU/)I,. <; J" uonnllP IrulI P'-Ul'lJ;>ld J 'IJ.
'~ I Ppcd )o p;oad~ \l Ol\" lIl1,' n'~'P<'ad~ lh,,\(un~
~Ifld :J;l,llU'II~ llla,,,dol~.\~ r> u l 9,.'11 UOueJlllf S 'IIll!U~I~Al'." rlD'U91ep 1I1fiu"I'.'0IM1n 1I()!l~I"'S'
.~ lpn' ~ 1~I~lll ~J r d pO ~l~lll '"
I UQ I1CP EA il l~"J q l lap IICu lS liq I'JP"'Jj~un
U'PlllaJ 11 JJ'lp~loJd IC~'I!;:I~" ~ JQ Al o r <.l " , ~ 'II S".~~Jlh:" ,',Whn'l"11 '(wfliri ':i )n UV\l~ "~)UO' I~~ 'l ~~II)lUJ<.I "I IUlI!P~ W
S'I"Irl~"qQH
UU!l I>IOS\'P 41 ...1 "PC IU ~I uOl ln!' p J ~l[1..l nJ ' UO\1I1,OS ~JOlS .""'qr. " '11
1I1O.l:;l·'1111lp..1W OnIIIlIIW"1I MII);)(I, ,,, \(1I A\ lV fW ~\11 O.l "n .'PPlII .)U"'IO,'
'~l P ~lll U011nIO~ ~11' u\ Peh IO.S'P .~," II , ~.tll J1JIJ IU»I') '\ till (I ! p~lrJ~llp..l
161 P"UJWJ~I~p
pue UC~ I ' 01 p.l.I""J~UeJl se... undl(.:lp.Ij'II<) <1U/ 0 [ P·"18, ,1·\\'IJlc.mnv
~ " USU y~ alii pu~ UOllnrOS :ll./tU1:$ 10 UOIlP.!IU~)UO) .001 "'II
UU ~~~Ij IUolJ.>H>P 110 pJIlIJOp.)d >I:''' II UUlsp.)Jd ,,)I'IP')JJI;;lll[ /Jo/I"I<>'< Ij;>U/S 10 JlOJIIH"d;}Jd

-P _ulul.Plap ~-~ JJj,jnq 1i/"1~\ld < D4oJ pile'!. lit!

"'\\ (l~ _, ~J;)1I1 pU~ U01IT"..Ilu,))um %001 ~ !"II11r $U0I-1"I<>'I ~11lt.u"", J ~ll"q " IE.IlP 'IJH N 1'0 UI 1I"~J.!p ~1'....' ulltl'18"UII 10 .{l'I'qnl"~ .><u.
1".)J~Jj\I' 'I' ~U!7·(te \l" ( II p auu o}J ;;O Sl I I 'PO!J;)d )J011~ H"" WOlll1,unJ ,(P"lf '(l/l"lnlQ5
~u\l~l~dn ~ w~, 10l P U<l j) D41;;IU JO UQ 1 Sn~ld ~ 41 ' 11~!1" 'I Allllqt.'lNd~'J I U;llll d o [;;~ ~I' POI Il'l W
UOI"J,~JJ

'1.UI.'J&.l!~U:>P lIl!Wl:J 8u'~n mU H,~JI.' Illllu:>pIII'M I~ 100 p~).UNl ,,;.\\

'J ldlll C, I I Q! ln [""'~ljl 0111 01 o\, OZ l l'U\" :-rUlIIU\!)'; pup All' <>I r" ,,')l)l1~ ""~M s.'lr lcl P')d OI').....)) .14.L alUPl.\'P JO lUlU at
~,0<I1 ''l\,O!J ,0
.l:/UI:.l ,Wllt!1IU{I 'UOJ '11\-" QUU'pp t pJfl'U"'~ alll."o:!O) m \In UOI"""!' 01 p;)..... oll" 'F." ~I ~IU J'fl " U\II O~ <l"." ~11"1 u~u",nllt><' ~4J.
.(q I1{1S"""~!' ~l'_\\ llUd tljrU!1 JQ ,{J ...,ro,l,I I U"::U..d ~'11. . _I ""AAO''''' 'I"IA t'LI.lu~oJUl·l nll~4l<1'U oISf4d "l'qow 'II'.... ;"allld"l~p ~U'PU~~I';OJ

I'L toOL I ',ZOl -/I ''''!irl 'S~ 10<1 'Ull UII} W. , DI/d (u olSV
Gl.!

rr
on
"
l'
~ 0
'" 0

•
»' . .
"'"
~,

..,"''' !
6166 C o t ~
l[,·v9l S'S I . 1I .•

•
• "'$<

r
- ~,
0

.-- • ,"-,
.- ~O
,,f•
• "s, ,
•
8T66 ' O ~ ,~
SUO·O- XHKlO ·A
.,
.," I
pueq/:lu st r -SZ p..Ie(lUltlS Ulldn 'il r.U!I)O "11-I~;lUn :l. ·)jl.'l
-- -

r
"/9-\: "So:JI.:!) [[Op nI OS ~1 ~\1I1'~ lIO!!nloSSI P
P"~ 1""1'''''1' wr!J) ulld,,:I'tU'1 )0 Jij Ie '~~MJ, qo W~'" '~"'~~Itl pln'
~uclq WQJJ s>I ""d J~'llu U.. Sf ;I!l'Nd, ~q {II puno/ W"," pOljPUl ')'IL
IIJ"rJOiJdS
--'­ SJ;}I;nUl,,",~d UOIl1!!PI1l<,\

( I ",q ~.i.l p.1J..l~PJd S~M ] ~ (h:~ .'~II'J CtlUltljJ\\ l~<n

J ~~WI pue .u'l l qcl!V.~ ""'" 10 ,)s"e~lI ~llnSJl ~ U!-"OIlQI 01 1"" 'H llU 10
S<ldlil ,noll~,' IIIUJj i~ OIIIlI05 p.n:pU~l~ P~,I;))llJ pur p.u.l'lIlun ~ ll1ljl 0!l
~)'Ir<IIIV'IU'O' lOlII:1

·.S"~I;:U ~!'I)P ~41 1,10 iluopu.>d;>p r~I.HI~9 ..J ....... UOO l pUO)
llld~ SL pur lW flO€> "lIP U1(1..1., -,,,,,,11 SL [lue wd,) OS J" p"",-,~ .)\Illr PUL'
I'" 00f> Pill' lUI O()~ JO JlllUIo.1 lfI"V. P''''I~,)IP S~,,, 1<llqrl,IO u"!l n lo~S ' (1
p;,vd, fW" J11I'1I",\

'tJII N 1"0 '~/" l~ lq"l u1ld!l:J~UI1

JQ U"llflluSS1P JO) I';)I~~I~~ wmp.lUl ;)111 -<l,)UJ Il '[ oI II>Jl""' ll'Ul Of.. '"
« ,Oil" b ~I lf~l Ul.101 ~lf!!'iOV ~llo, "~~~I"J "l. ' ~ "Wl\" I" UQ UnIO< ' ,!P
JOt rll.~llJ:) O,)U"ld~JJC ~Il' · S' ~ fld J "~Jln 'l ~1~4 d$o'l" " Ill U! I'U~ J,lll" q

n I OL I 'lZOZ '8 ;'RSS/ 'S I/uil 'sal/ uri' uu u'IJ I [[<l/SI'

~/WD(J PUI> ~msu"d
i.:.l

PUI'tjf!u OS
P1I\''1/11" OS
U"'I'IIO~ P_Il;PUC1S
UOIlTl[OS ~[dule~ ,
./

UUIl!PIlUJ

~f' O ~/WI.U LL
(,t.'O S!UJUI r L
SOOt
t (,1)
WU 9&7
wu l,{,l ,
I) n "1111 ZZ
(n UII4l tiL
19'1
Ls'r
(If,-,z'r S'<)I '~lIo)nlOI IOU"~)')11
r"/·'frl·l' LJ oU~1110 11"m'IjF' W .,
MlOSU% Jl.l<I H OSU o;. SJ.))<1Wc.Jl'd

lit 77.0 0'0

(tOO'O
OO?O
;;O~ 0 ,
'"
S6'!IQII! pu~q/l!u O~
Eb~TI'I p,aoq/S" OS J'ILHI
aSM% p;mOd~lllnowv UOlllpUOJ

H.Olro rOl'() ,
'" u "nr.UU.)~UoJ

Ol 6lZ<OOI J'11<1H
'"
OS1l %
(L

J(Jl'unlp~\l1 uOl1nlo s.!p r.' lJ~I" ~ O ~l '~~II'1 ~pm ll fiJI J~1l r;~ P" HJJop~(1
PUPQ pll~<I
' 17·' l'OlOO1W JU IIOI1l'PIII:II 'tr.n
,aJl1~~UDu~1l0
J1Ld H ~lItS" Ino p~I.uC) sr."
ptl'['
'p;:>2lw))\lv pu r p~\J"'I':M;lp n'''' pOq);)lU UOllr["SS'p .)I{l (CO(.o f.lu 011 /'Ju OS o/~OC: ' ,
NOI S[llJNOJ l'J'i,6
pUl'q
/ll u 00 1
pUfq
/~II U"
pll~q :r1.l.<l1l
"",(fO I ,
'UIJIl 'P""J S!'11 Hpun II Z .IUJ P dwJlI Un~ 1I~f) ~~'1 All]!qel>
~ ,'6& pu~q/~" 06 f!" OS %08
\I<'II\1l10~ ,n" !~ ",m(p~(u UOp l1 llNilP ~~ ~I,< rllns '! ).Lf. ' " 1:.1 11 N (' 0 '~mu
A.. ~"'QJ'U I).)\lo ds p.ll ods
'1, ( III 1.011-09 JO ....Ol ..." 'dul'll PU(' 1)11 N 1'0 10 1l00jIPI"" ~S.lJl~
U' '*,5t l"oqP ~q .. p p.f:!~ p 0 1 p~l.Iod"" 1I.);,q seq 11 :l !.f 'I1H " 1010 % lU nOtu \, lllno",\, p O'lI.)h' I.)"..q 'O'I/'S
U<1!I'PUC~ I" JII1I ,S J'l 0 1 pun OJ ~" M 1IIl dtr11ru!I Jill 'IUI OU(i II> ~llInl(lh
111'''' p.l'\,I,l'qQ 8SPJ!,),I J-'l hlq \nq lln5<U MoPq~ll c~ ",\I'll IIU ODS' 10
~,unto~ 'Ill'" U"!l'fluo~ :)UI"~ nlll';).I01W;)'lun:! ·191 ,n
1'1\,,'611'1"1 ~J"tlI
1I011tpU" 1 OUI W,)J J lU~J~II' p S~M I\II 0 0 1'> 10 :)1"" I"APUt 'Wdl SL 'Tl lr ;rdJI'
,,
"...
;01"'.1.1 - UH N I '0 lump~IU ~ql sr_" UO IUpUOJ uounl0Sl'II' ,Jill 'il.l.!H
S6L{' 1U1,r3r! 11 !urf/hiS Mll
"u/lfriOI Iwjltrt 5
OOl6 11II~16 (lII/J1h M """"
%rni
-:<:;~% U<:>pIUlUa;lUOJ l/Ofll'-llua;lur» POII"'W , ~,
'ON'S
'(L",ql ,l~"nlloJJ
sc a, I~" Plllll'J sIIOl<JJ ~\P pu C ~ lq~l S ~q 0 1 JI~ nlJ.I a"~,,, s.)l'IUI'" ;'11.1 [Anl k E1n'~\I :z ~lq~ .1

,(J'M"Jl jJ011llJOS
t pu" Z So'Jf)P.1. Ul UW)qs
.(<> "IY~l) Isn'lOJ ~\i 0] u;).\O,,,1 so,,,
pm[l~W '~)U:)H '\11Il1 11II111)M ~ SI pur p.')rl'u I~.) ~EM IJ~ ~ I \j~eJ Ie ,('J,\(I)JJ % 311l '%O? I PUI' 'no I 'Ol:l
OJ PUf,"! SCAI An 1".1 aJlJc"+,o sQ r. pu ~ T Il.<IH JOJ C N~ l1.~ad I" "~"-'~"'\' J" S\a.\al n~J~\ ll' .()''''''J~J % ~~I ~l!'Ull!lJJPP ,(q rJ\~UIIII~ ,b r .II1J.lI' JIU
1I01U"11,'W1 tuOJJ P;)UIMq O asl.l % re lSOq OJ "<I Ol puno) Sf!.'" P"41:)1U OlU. JUWIIJJV
,,<Jtll<''','I(/
(b' t ·$~I.:l) .~ ~,\Il:J;J~'.)J
(s pur t >,1\qOUJ .......nnOI sr.)q on pllnOI se.. . q~!4'" LIOI~,,~~d '1:116&'01"''' 6Z6t>0 "'I Ul punOJ \U\" I" Jnl"A ~U lwflhl ~t"1· <:I: 11"'" 5~
''l~IP~'''J.l ''l\1ll'u~ ll'I'Q ~ltJd "J ":')I", "~~" d ~i ", ..,\ r DI110<t ' JD un" 'Jil.l!l ~<I ,I. r lll' '1.,Mu ~? t-S(': )!> ...\i" o:.i 1J!>nE!.II(l.UlI(" ~ 11 NAO p;>ul~ lq'l "11M AluF,'m ; ,lOU
u,"~,~ N !Jlr.>ll!1

I-LI -O, t 'llO Z'8 '1nSSI 'SlI OA 'salJ IJI/J fU.' '''1J ( ""1St'
 POllsort ami Domlc
As."" J Phfll'm a", H~$, Vol 15, I$SU~ 8. 20;U , / 70· ,,.
5 m)(l ln"l'tlip tln r~ ble l .....JS 0, 1 N HC) and th~ " p p ~ rMu s \I~C~ was pJddl e In" !tlil 1'. 14 A,.1!lablc from tm f" - '''''I'" ,''(">'t.",,<J.'I~ 1,1..11'"
( t~'I'~ I ) Th~ opt",,,,m ;peed and ' Glume selected wert" 75 rpm ~nd
drup.ltlJa dues n<42(l12,'201: ~ IOr'g I ,I)(JOCh ~" IR pM
.1 n ... hnw"~~r P "1 , 1''''''31:';U Bi" I,hvma..:cuI,,-'.and ph;um2C"l;'>t1".
9 00 ", I, rel pN1iwly, 1' h~ propo"'\1 m~thod wa, valld1t>ld with rc'r",n
~ Ir~al;'" J"~~I Indu. V.II.,bh rr,,}.n, lull : 2(1 1<1, r,.l~~
10 I'.,,~,"el~"" Such .os s JH!C"lfltilY. hneanly. accur.u),. r ret:"iuu...nd ~ t>rc...."T;~n J f..rnmc. J l'hann :>,cul" . 1 l)""",huI<'" I,"U "!!
r()h u, :"~." T h~ m~t hod wa~ lou no1 \ (J b~ ,,!,ecilk . Ilnc~ r, ~nd r()bu~t , l,n Ll<'<l " ,~gdc," , To) l ora~d Fran"" Gr()\l~. ~()t) ~ r 4 1'1-3:
/, En/lel II.F. 9.• rdcn\T, C Ul1p:.nh.uo ~( OIcJt.ir~':-'. \',I,,:.t•• ' \1
AC KNO W LE DGME NT ~hJpt" 11 n [',aluJ1Lon "r ImJ31Lrltl1 1l .." ,IUl,,)n h"rn .a',lcl< ",.n~
1I1'l.(" .,cd llV m",ht.>d, [)I"~ "'nal Reo "U I9-,.4Ii-.'0
Th~ .l,,' hon; ,"~ thankful [" .\I SS\l~ College "r Ph~rm~~y, Pu n('. fur 7 Inl"l"Twl"on.! Conf(",,,.:,· on Hanrt<>H 17.""" H( II I 01 I shllLu!
I' ''''lding n~<:C~lklrv
. 1,,(lhtte~ hi carry. out lhls wur\( RC'<ju"""l('nI" r,1r R~~NratiCn 01 I'hurrrL~ct'\!!Lt . l, r"l tlun' n \. ".
V.lllda· "II of .\nai>,,,al Pro<...,d"r" TC~1 30d Melh..'rlo,,,~) 'Q~1t II
AUTII ORS' CONTRI BUT IONS ~"'IIl'lIJ"d. ~Q(l5 , p, 11-5.10
~ (j"""'"ut"n ,.i in,JoJ. M"\I<"), Qf H"ollh "ll(>onac<'f'Io."" ~ "I' in()':'
M" f:hatl~ r~n~~re studie d, (" rri ~d oul Ih ~ r~srarch WOl'k. ;m d drJftcd \,,1 ~~~. ~ H 7 Ind, . 1'h~ !"J, .• n f' hnrmaC()p<h".1 , :O!~ p :-t
th., man u,crlpt IInder the i!" ld .. nct ofMrln~lIni O" m!t. Th l' ntanu>cnpl Q. rt..;, n"",IUl"'" " roc«lurc. I):;'iclopmcnt \~1t6JI',.~, II)'))
"" ~ d,erked ,,~ d JPpL'o~'e,j by M,rn ~h'H D"",le. r 1-'3_ ,\,~;13blc from 1m.,. l ~tam-cJ" ""I' "f\; "r-.-"'" ''1'
upl"",], ~O~ I ill!. 1092 pJi (u." ...""-,,,',I.m 2f\~(J Ike III I
CON H ICTS O F INTEREST In n ..l " ut •.;.n f~jl!"~ ~"d AC~~1'13n.-c (. Ulcn:\ IN [mm"h~l~·,da""
S(ll,d 0),.1 [)o'~g~ fonn Drvjl Pn'(liJ CI' \..()" r.tntn l! HL Vh o;;('>JIIOtlll, j),W
Th~ ~ 1!1hor. ,l~h red that Ih~y h;w,' nn ,"I)nnl,:I, of Infer;>sl. Sub'l ",.:~ Cwd....ce f.... lndu~try. L:SA. L' S Ot:p.:onmcmulll."',h ~ml
ll",n~'1 S<:rv;cc, r<><Xi ~ L1d dn,~ J<imin;"',, (",n Zll! ~ p ~-~ \\J,1.1hk
AUT HORS' FUNOr."~G lrom hup" ,,'~w Ida go" I;I..... .-drug.~ I,uh l"hro 1.>",oIu'l"" Te,·",!,
~nd -A" ~cplJ1LC~ -c n1 ~ tla- fi If- hun .<:JISIe· I( el ca. ~ "0!r<l-Ora I ')oa, ,'g"
\ <'1 lunds wt"1"e r«elv.. d fr<'lm J "Y ~f!~ncy. hon\1-0rug_l'rl'duc\ •. Ct)n~tmn[t_ H.t~h_5..' lu b llll).·_Oru~ ' ~LJb",'n~~­
_(,u.<I"n,·~_ f"r·l"t!u'Ir'"pdf
RErER IoNCES I I BOOk RP_ \\a" H ,~k ~ ll . Pl nliey M Stab, I,ly 'rdLCll , n~ IfPTIJ
m.;tlk..J lor ',"IUJtll1~''''''' c'$l!1n.lf,,,n ot cmf"l~hl1nflA:mJ Ir";;:"r"~
r"ro lh, Kl) 1-",enlla l, ,'I Mcd,~~ 1 of \/ed lcal Ph~ml~,,,I,,I'Y' ~ . N. ;Il ph"rnt,KCLII,"~1 fc.m' LL I~I IOLl , ",,,,,I Own, L.'tt :('17.' 'I\-~~
hl<:hu J ~~~c Bnuht'f, \kd;call'ubhg,.,,,,; ~019 p 1()()J_2HO.~<17_ ..1,,,- I!J If\l\o.~~!·pn8 21)17 1 ~79 %'
)-.JI L',n,,1 L.thlo t)' "I ~ k J l ctn, ru b( h~m ("(tmpO "r.J Summ:l!) fu r l~ \JtI!ul~I'ali KR A lt~.-1e P. U"(ld l d~ 5 Sl.'t>.lil~-md!<~t'"T~ ,,!tra
('lD It)(I'J'' 14~, l.maghrl!n Bc,j,e<J.J IMI)). 'auvnal l~nle, I" , pcrt"flnan~~ 1'<1",<1 ,-h ,c~n~'",,"'pl, ; lnel h•.d ",',~I,,~' ,,\:,,\ 1".1
Bl[)twhn~I,'~\ Inrunnallon. 10().1 ", hd~H"n h,,- snnuh.. m.,\lu, c,t'lIlatoo" " r m~Hvm,," I"",~llr''''.
J .".•,:Ionngcr I "gdh~'m H,ghl'~hl' ot rrc,c,ib.no:. Infotm"")fI i\., tmp"dltl,l7Ht ulld lI\ b"l~ ~",i ph.lrm.",:euu,.,1 do"'~~ l<" l~l H,,'nl.·,!
r"'d.I~"I ~ I h",,_~hrl"'\ Tlbl~'~ nL.. hrol\~e, I n~"~ nn f'tI~m""..,uu,,~I, C1m"JIO~r ~C)~ I. )s ·d hl\!. do, . 1(1111112·1>0>, ~(jl'l p\U n 1 '1#.w~

i l 'l