Accessed from 10.6.1.
1 by spen3tkzy on Mon Jul 24 06:13:42 EDT 2017
USP 40
layer chromatographic plate (see Chromatography 621)
coated with a 0.25-mm layer of chromatographic silica gel
mixture. Dry the plate with the aid of a stream of cool air.
Position the plate in a chromatographic chamber, and de-
velop the chromatograms in Solvent mixture until the solvent
front has moved about three-fourths of the length of the
plate. Remove the plate from the developing chamber, mark
the solvent front, and allow the solvent to evaporate in a
stream of cool air. Examine the plate under long-wavelength
UV light. Mark the principal and any secondary fluorescent
spots. Spray the plate with Detecting reagent, and mark the
principal and secondary blue spots. Compare the intensities
of any secondary spots observed in the chromatogram of
the Test preparation with those of the principal spots in the
chromatograms of the Standard preparations: the sum of the
intensities of secondary spots obtained from the Test prepa-
ration corresponds to not more than 5.0% of related com-
pounds.
Assay[NOTEConduct this procedure with a minimum ex-
posure to light.]
Mobile phase, Solvent mixture, Standard preparation, and
Chromatographic systemProceed as directed in the Assay
under Methylergonovine Maleate.
Assay preparationPlace 10 Tablets in 1 500-mL volumet-
ric flask, add 400 mL of Solvent mixture, and shake by me-
chanical means for 15 minutes or until completely disinte-
grated. Dilute with Solvent mixture to volume, and mix.
Allow the solution to settle for not less than 30 minutes
before use, and then filter to obtain the Assay preparation.
ProcedureSeparately inject equal volumes (about 10 L)
of the Standard preparation and the Assay preparation into
the chromatograph, record the chromatograms, and meas-
ure the responses for the major peaks. Calculate the quan-
tity, in mg, of methylergonovine maleate (C20H25N3O2
C4H4O4) in the portion of Tablets taken by the formula:
(L / D)(C)(rU / rS)
in which L is the labeled quantity, in mg, of methylergo-
novine maleate in each Tablet, D is the concentration, in g
per mL, of methylergonovine maleate in the Assay prepara-
tion, based on the labeled quantity per Tablet and the ex-
tent of dilution, C is the concentration, in g per mL, of
USP Methylergonovine Maleate RS in the Standard prepara-
tion, and rU and rS are the responses obtained from the As-
say preparation and the Standard preparation, respectively.
.
Methylphenidate Hydrochloride
C14H19NO2 HCl 269.77
2-Piperidineacetic acid, -phenyl-, methyl ester, hydrochlo-
ride, (R*,R*)-()-;
Methyl -phenyl-2-piperidineacetate hydrochloride;
(RS)-Methyl-2-phenyl-2-[(RS)-piperidin-2-yl] acetate, hydro-
chloride [23655-65-4].
Official from May 1, 2017
Copyright (c) 2017 The United States Pharmacopeial Convention. All rights reserved.
Official Monographs / Methylphenidate 5111
DEFINITION
Methylphenidate Hydrochloride contains NLT 98.0% and
NMT 102.0% of methylphenidate hydrochloride
(C14H19NO2 HCl), calculated on the dried basis.
IDENTIFICATION
A. INFRARED ABSORPTION 197M
B. IDENTIFICATION TESTSGENERAL, Chloride 191: Meets
the requirement for the silver nitrate precipitate test
ASSAY
PROCEDURE
Buffer: 2.7 g/L of monobasic potassium phosphate
Mobile phase: Methanol and Buffer (1:2). Adjust with
phosphoric acid to a pH of 4.6 0.1.
System suitability solution: 0.005 mg/mL of USP
Methylphenidate Related Compound A RS and 0.5 mg/
mL of USP Methylphenidate Hydrochloride RS in the
Mobile phase
Standard solution: 0.5 mg/mL of USP Methylphenidate
Hydrochloride RS in Mobile phase
Sample solution: 0.5 mg/mL of Methylphenidate Hy-
drochloride in Mobile phase
Chromatographic system
(See Chromatography 621, System Suitability.)
Mode: LC
Detector: UV 209 nm
Column: 4.6-mm 25-cm; 5-m packing L1
Flow rate: 1.0 mL/min
Injection volume: 10 L
Run time: 2 times the retention time of
methylphenidate
System suitability
Sample: System suitability solution
Suitability requirements
Tailing factor: NMT 3.0 for the methylphenidate
peak
Resolution: NLT 2.5 between methylphenidate re-
USP Monographs
lated compound A and methylphenidate
Relative standard deviation: NMT 2.0% for the
methylphenidate peak
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of methylphenidate hydro-
chloride (C14H19NO2 HCl) in the portion of the sample
taken:
Result = (rU/rS) (CS/CU) 100
rU = peak response from the Sample solution
rS = peak response from the Standard solution
CS = concentration of USP Methylphenidate
Hydrochloride RS in the Standard solution
(mg/mL)
CU = concentration of Methylphenidate
Hydrochloride in the Sample solution
(mg/mL)
Acceptance criteria: 98.0%102.0% on the dried basis
IMPURITIES
RESIDUE ON IGNITION 281: NMT 0.1%
Delete the following:
HEAVY METALS, Method II 231: NMT 10 ppm (Official 1-
.
Jan-2018)
ORGANIC IMPURITIES, PROCEDURE 1
Buffer, Mobile phase, System suitability solution,
Sample solution, Chromatographic system, and Sys-
tem suitability: Proceed as directed in the Assay.
Analysis
Sample: Sample solution
Identify each impurity using the relative retention times
in Table 1. Calculate the percentage of each impurity
 Accessed from 10.6.1.1 by spen3tkzy on Mon Jul 24 06:13:42 EDT 2017

5112 Methylphenidate / Official Monographs USP 40

in the portion of Methylphenidate Hydrochloride Suitability requirements

taken: Resolution: NLT 2.7 between methylphenidate re-
lated compound A and phenylacetic acid; NLT than
Result = (rU/rT) 100 3.6 between phenylacetic acid and erythro isomer
Tailing factor: NMT 2.0 for the methylphenidate
rU = peak response for each impurity in the Sample peak
solution Relative standard deviation: NMT 2.0% for the
rT = sum of the responses for all impurity peaks methylphenidate peak; NMT 5.0% for methylpheni-
including the methylphenidate peak in the date related compound A, phenylacetic acid, and
Sample solution methylphenidate hydrochloride erythro isomer
Acceptance criteria: See Table 1. Analysis
Samples: Standard solution and Sample solution
Table 1 Calculate the percentage of any individual impurity in
the portion of Methylphenidate Hydrochloride taken:
Relative Acceptance
Retention Criteria, Result = (rU/rS) (CS/CU) (1/F) 100
Name Time NMT (%)
Erythro isomera . 0.58 0.15 rU = peak response for each impurity peak from the
Methylphenidate related compound Sample solution
A 0.85 0.5 rS = peak response for the methylphenidate peak
Methylphenidate 1.0 from the Standard solution
Any individual, unspecified impurity 0.10
CS = concentration of USP Methylphenidate
Hydrochloride RS in the Standard solution
Total impurities 1.0 (mg/mL)
a. (RS)-Methyl-2-phenyl-2-[(SR)-piperidin-2-yl] acetate. CU = concentration of Methylphenidate
ORGANIC IMPURITIES, PROCEDURE 2 Hydrochloride in the Sample solution
[NOTEPerform this test only if ethylphenidate or bis- (mg/mL)
1,2-(-carboxymethylbenzyl) piperidine is a known pro- F = relative response factor (see Table 3)
cess impurity.] Acceptance criteria: See Table 3.
Buffer A: 5.7 g of monobasic ammonium phosphate
and 1.6 g of 1-octanesulfonate sodium in 1 L of water Table 3
Buffer B: Add 4 mL of triethylamine to 1 L of Buffer A. Relative Relative Acceptance
Adjust with phosphoric acid to a pH of 2.9. Retention Response Criteria,
Solution A: Acetonitrile and Buffer B (7:43) Name Time Factor NMT (%)
Solution B: Acetonitrile and Buffer A (4:1)
Methylphenidate
System suitability solution: 0.5 mg/mL of USP
related compound A 0.55 1.1 0.2
Methylphenidate Hydrochloride RS; and 3 g/mL each
Phenylacetic acid 0.67 1.0 0.1
USP Monographs

of USP Methylphenidate Related Compound A RS,

phenylacetic acid, and USP Methylphenidate Hydrochlo- Erythro isomera . 0.80 1.0 0.2
ride Erythro Isomer Solution RS in Solution A Methylphenidate 1.0
Standard solution: 0.5 g/mL of USP Methylphenidate Ethylphenidateb 1.22 0.9 0.1
Hydrochloride RS in Solution A
.

Bis-methylphenidatec 1.80 2.6 0.1

Sample solution: 0.5 mg/mL of Methylphenidate Hy-
.

Any individual,
drochloride in Solution A. [NOTEAllow the solution to
unspecified impurity 1.0 0.1
stand for at least 2 h.]
Mobile phase: See Table 2. (See also Chromatography Total impurities 0.5
621, System Suitability). a (RS)-Methyl-2-phenyl-2-[(SR)-piperidin-2-yl] acetate.
.

b Ethyl -2-phenyl-2-(piperidin-2-yl)acetate.
.

c 1,2-Bis(carboxymethylbenzyl)piperidine. [NOTEAlso known as 1,2-(-

Table 2
.

carboxymethylbenzyl)piperidine.]
Time Solution A Solution B
SPECIFIC TESTS
(min) (%) (%)
LOSS ON DRYING 731
0 90 10 Analysis: Dry a sample in a vacuum at 60 for 4 h.
7 65 35 Acceptance criteria: NMT 0.5%
10 50 50
12 50 50 ADDITIONAL REQUIREMENTS
PACKAGING AND STORAGE: Preserve in well-closed
13 90 10
containers.
16 90 10 LABELING: If a test for Organic Impurities other than Proce-
dure 1 is used, then the labeling states the procedure
[NOTEEquilibration of the chromatographic system at with which the article complies.
the initial conditions for a minimum of 30 min is rec- USP REFERENCE STANDARDS 11
ommended before the first injection.] USP Methylphenidate Hydrochloride RS
Chromatographic system USP Methylphenidate Hydrochloride Erythro Isomer Solu-
(See Chromatography 621, System Suitability.) tion RS
Mode: LC This solution contains 0.5 mg of methylphenidate hy-
Detector: UV 220 nm drochloride erythro isomer per mL in methanol.
Column: 3.9-mm 15-cm; 5-m packing L7 USP Methylphenidate Related Compound A RS
Column temperature: 40 -Phenyl-2-piperidineacetic acid hydrochloride.
Flow rate: 2.8 mL/min C13H17NO2 HCl 255.74
Injection volume: 10 L
System suitability
Sample: System suitability solution. [NOTEIdentify the
peaks using the relative retention times in Table 3.]

Official from May 1, 2017

Copyright (c) 2017 The United States Pharmacopeial Convention. All rights reserved.
Accessed from 10.6.1.1 by spen3tkzy on Mon Jul 24 06:13:42 EDT 2017
USP 40
.
Methylphenidate Hydrochloride Tablets
DEFINITION
Methylphenidate Hydrochloride Tablets contain NLT 93.0%
and NMT 107.0% of the labeled amount of methylpheni-
date hydrochloride (C14H19NO2 HCl).
IDENTIFICATION
A. INFRARED ABSORPTION 197M
Sample: Equivalent to 50 mg of methylphenidate hy-
drochloride from a portion of powdered Tablets in a
40-mL centrifuge tube. Add 10 mL of chloroform,
shake, and centrifuge. Filter the clear extract through a
medium-sized sintered-glass funnel into a beaker, and
repeat the extraction with an additional 10-mL portion
of chloroform. Evaporate the combined chloroform ex-
tracts on a steam bath to dryness. Agitate the dried
residue with 2 mL of acetonitrile, and filter the mixture
through a small sintered-glass funnel. Wash the crystals
with an additional 2 mL of acetonitrile, and dry them
with the aid of suction.
Acceptance criteria: Meet the requirements
ASSAY
PROCEDURE
Buffer: Dissolve 1.6 g of anhydrous sodium acetate in
900 mL of water. Adjust with acetic acid to a pH of 4.0.
Dilute with water to 1 L.
Mobile phase: Methanol, acetonitrile, and Buffer (4:3:3)
Internal standard solution: 0.4 mg/mL of phenyl-
ephrine hydrochloride in Mobile phase
Standard stock solution: 0.2 mg/mL of USP
Methylphenidate Hydrochloride RS in Mobile phase
Standard solution: Mix 10.0 mL of the Standard stock
solution with 5.0 mL of the Internal standard solution
Sample stock solution: 0.2 mg/mL of methylphenidate
hydrochloride from finely powdered Tablets (NLT 20
Tablets) prepared as follows. Dissolve in Mobile phase
using 70% of the final volume. Sonicate for 15 min,
and cool to room temperature. Dilute with Mobile phase
to volume. Pass a portion of this solution through a
suitable membrane filter, discarding the first portion of
the filtrate. Avoid the use of glass filters. Polypropylene
filters are suitable for use.
Sample solution: Mix 10.0 mL of the clear filtrate from
the Sample stock solution with 5.0 mL of the Internal
standard solution.
Chromatographic system
(See Chromatography 621, System Suitability.)
Mode: LC
Detector: UV 210 nm
Column: 4.6-mm 25-cm; packing L10
Flow rate: 1.5 mL/min
Injection size: 50 L
System suitability
Sample: Standard solution
[NOTEThe relative retention times for phenylephrine
hydrochloride and methylphenidate hydrochloride are
0.8 and 1.0, respectively.]
Suitability requirements
Resolution: NLT 2.0 between the analyte and the in-
ternal standard peaks
Relative standard deviation: NMT 2.0% from the
peak response ratios of the analyte to the internal
standard
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of methylphenidate hydro-
chloride (C14H19NO2 HCl ) in the portion of Tablets
taken:
Result = (RU/RS) (CS/CU) 100
Official from May 1, 2017
Copyright (c) 2017 The United States Pharmacopeial Convention. All rights reserved.
Official Monographs / Methylphenidate 5113
RU = peak response ratio of the analyte to the
internal standard from the Sample solution
RS = peak response ratio of the analyte to the
internal standard from the Standard solution
CS = concentration of USP Methylphenidate
Hydrochloride RS in the Standard solution
(mg/mL)
CU = nominal concentration of Methylphenidate
Hydrochloride in the Sample solution
(mg/mL)
Acceptance criteria: 93.0%107.0%
PERFORMANCE TESTS
DISSOLUTION 711, Procedure for a Pooled Sample
Medium: Water; 900 mL
Apparatus 1: 100 rpm
Time: 45 min
Analysis: Determine the amount of methylphenidate
hydrochloride (C14H19NO2 HCl) dissolved by using the
procedure in the Assay, making any necessary volumet-
ric adjustments.
Tolerances: NLT 75% (Q) of the labeled amount of
C14H19NO2 HCl is dissolved.
UNIFORMITY OF DOSAGE UNITS 905: Meet the
requirements
ADDITIONAL REQUIREMENTS
PACKAGING AND STORAGE: Preserve in tight containers.
USP REFERENCE STANDARDS 11
USP Methylphenidate Hydrochloride RS
.
Methylphenidate Hydrochloride
Extended-Release Tablets
USP Monographs
DEFINITION
Methylphenidate Hydrochloride Extended-Release Tablets
contain NLT 90.0% and NMT 110.0% of the labeled
amount of methylphenidate hydrochloride (C14H19NO2
HCl).
IDENTIFICATION
A. INFRARED ABSORPTION
Sample: Place a portion of powdered Tablets, equiva-
lent to 100 mg of methylphenidate hydrochloride, in a
100-mL beaker. Add 20 mL of chloroform, stir for 5
min, and filter, collecting the filtrate. Evaporate the fil-
trate to about 5 mL. Add ethyl ether slowly, with stir-
ring, until crystals form. Filter the crystals, wash with
ethyl ether, and dry at 80 for 30 min.
Acceptance criteria: The IR absorption spectrum of a
mineral oil dispersion of the crystals so obtained exhib-
its maxima only at the same wavelengths as those of a
similar preparation of USP Methylphenidate Hydrochlo-
ride RS.
B. The retention time of the major peak of the Sample
solution corresponds to that of the Standard solution, as
obtained in the Assay.
ASSAY
PROCEDURE
Mobile phase: Dissolve 2 g of octanesulfonic acid so-
dium salt in 730 mL of water. Adjust with phosphoric
acid to a pH of 2.7. Mix with 270 mL of acetonitrile.
Solution A: Acidified water; adjusted with phosphoric
acid to a pH of 3
Diluent A: Acetonitrile and Solution A (25:75)
Diluent B: Acetonitrile and methanol (50:50)
System suitability solution: 80 g/mL of USP
Methylphenidate Hydrochloride RS, 1 g/mL of
methylphenidate hydrochloride erythro isomer from
USP Methylphenidate Hydrochloride Erythro Isomer So-