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STABLE ISOTOPELABELED STANDARDS


1

COMPARISON OF DEUTERIUM, 13C AND 15N ISOTOPIC LABELS IN MASS SPEC INTERNAL STANDARDSScott W. Landvatter and Rich Tyburski

INTRODUCTIONClinical applications of LC-MS/MS have risen steadily over the last ten years. MS-based methods to quantify key biological components have been based on the improved sensitivity, specificity and throughput of the LC-MS/MS. Stable isotope-labeled internal standards are important features of these assays, helping to optimize the accuracy of the method, providing accurate results.

However, the first generation of stable isotope labeled internal standards had the drawback of relying on deuterated compounds, which were readily available and relatively inexpensive. Procedures and Standard Operating Procedures (SOPs) were established and clinical assays were performed with these first generation deuterated standards.

A second generation of labeled internal standards is readily available, characterized by 13C and 15N labeling or, in a few cases where there is no viable alternative, deuterium placed into stable, non-exchangeable positions.

The Vitamin D assay shows the progress made in the synthesis of labeled internal standards. This assay was among the first to switch from RIA (radioimmunoassay) to LC-MS/MS and is now among the most widely performed LC-MS assay.1 The first available internal standard was 25-Hydroxyvitamin D3-[26,26,26,27,27,27-d6].(see figure 1)

In light of the availability of a second generation labeled internal standards, the question arises as to which is “the best” internal standard for LC-MS/MS assays1

More recently, two 13C labeled forms of 25-Hydroxyvitamin D3 have become available.

25-Hydroxyvitamin D3-[26,26,26,27,27,27-D6] 25-Hydroxyvitamin D3-[6,19,19-D3]

Figure 1

25-hydroxyvitamin d3-[26,26,26,27,27,27-d6] 25-hydroxyvitamin d3-[6,19,19-d3]

Figure 2

25-hydroxyvitamin d3-[23,24,25,26,27-13C5] 25-hydroxyvitamin d3-[25,26,27-13C3] 25-Hydroxyvitamin D3-[23,24,25,26,27-13C3] 25-Hydroxyvitamin D3-[25,26,27--13C3]


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ISOTOPE LABEL CHOICEDeuterium LabelThe use of deuterium labels can lead to challenges during analysis. First and foremost is the possibility of deuterium loss from the internal standard due to exchange with hydrogen (protons). This can occur when the deuterated compounds is in solution or in the mass spectrometer and will be detailed in a case study with aldosterone.

Loss of deuterium compromises the accuracy of results obtained with the labeled internal standard and has two scenarios. First, the deuterated internal standard may lose all of its deuterium, thus giving rise to a “false positive” where the internal standard appears to be the unlabeled analyte. However, this should be obvious to the analyst since the internal standard signal would not be detected.

Second, and far more consequential, is in instances when the internal standard loses 15-20% of deuterium over the course of the assay. The internal standard is used to standardize the concentration of the analyte and if this internal standard signal is not reproducible sample to sample, its instability will lead to reporting of erroneously high analyte concentrations. Unlike scenario one, this is more difficult to detect.

A further complication in the use of deuterated compounds is HPLC co-elution problems. Deuterium is less lipophilic that hydrogen, and this can result in the deuterated standard not co-eluting with the unlabeled compound 2,3,4

Carbon-13 LabelLabeling with 13C has none of the disadvantages of deuterium labeling. Carbon-13 can be obtained in high isotopic purity (99.5%) for introduction into the labeled standard, while specifications for deuterium are typically 98%. Carbon-13 is chemically stable; there can be no loss of 13C via exchange with 12C. This gives a very clean, sharp molecular ion in the final labeled standard. Furthermore, there are no co-elution problems in HPLC between the labeled and unlabeled versions of the same compound.

The only disadvantage is that more elaborate syntheses are usually required to introduce 13C, and as a result, the compound may be more expensive. For new assays, the higher cost of the internal standard is frequently offset by the reduced time spent on initial method development and qualifications.

Other LabelsNitrogen-15 (15N) offers the same advantages as 13C. Its use is more limited since there are fewer options in positioning the nitrogen.

Though oxygen-18 (18O) is also available, and offers a molecular weight gain on +2 amu per atom, it, unfortunately, is also easily exchangeable. The 18O in accessible functional groups (acids, esters or ketones) is readily exchangeable, so 18O is rarely used.

CASE STUDY IN SOLUTION STABILITY – ALDOSTERONE

BackgroundAldosterone is a mineralocorticoid steroid hormone that plays a key role in the regulation of blood pressure. Aldosterone tends to promote sodium and water retention and lower potassium concentration in plasma. Regulation of aldosterone is a key feature in several antihypertensive medications, such as Lisinopril.

Primary aldosteronism (hyperaldosteronism) is a result of an increased level of aldosterone that exacerbates retention of sodium and loss of potassium. Hyperaldosteronism increases water retention and blood volume, resulting in an increase of blood pressure. The opposite condition, hypoalderonism, can also exist and is characterized by decreased levels of aldosterone.

Measurement of aldosterone in blood is therefore of prime importance when managing hypertension. The concentration of aldosterone can now be analyzed by LC-MS/MS.5 This method avoids the drawbacks of the more traditional measurements of steroids by immunoassay, such as a lack of specificity that can result in overestimation of the serum concentration of the steroid analyte, aldosterone.

The ChemistryDeuterated aldosterone, available since 2004, exists in solution in equilibrium between two forms in roughly 60:40 ratio.

Figure 3

The mass spectra of the unlabeled and labeled standards are shown in Figures 4a and 4b. The top spectrum shows unlabeled aldosterone with the M+H molecular ion seen at m/z 343.16. The lower spectrum shows the deuterated aldosterone internal standard. This exhibits an M+H molecular ion at m/z 351.22, which corresponds to a d8 isotopomer (60.7%). However, as is typical for a deuterium labeled compound, several other isotopomers are present. There is a significant amount of M+7 (m/z 350.19, 32.6%) and M+6 (m/z 349.14, 5.5%). The actual incorporation of deuterium in this standard is 7.5 d/molecule with M+8 being the major isotopomer. Additionally, the intensity of the M+8 molecular ion peak is significantly less than the unlabeled molecular ion peak even at identical concentrations in solution.


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THE ANALYTICAL SOLUTIONWhen used as an LC-MS/MS internal standard, the possibility of deu-terium loss mandates the analyst verify the integrity of the internal standard. Is the deuterium retained or lost once it is in the final me-dium for analysis? Is the deuterium stable over the length of time for which it is intended to be used? These two critical questions often go unanswered and can lead to the reporting of erroneous results.

There are two approaches to avoid this problem. One is using a 13C labeled form of aldosterone and the other is to place the deuterium is non-exchangeable positions. The preferred approach is to use 13C, since there is no chance of 13C loss and hence, no need for a validation study on the integrity of the label. The challenge of this approach is the difficulty in synthesizing 13C-labeled aldosterone.

Instead, a second generation deuterated aldosterone internal stan-dard that places the deuterium in completely non-exchangeable positions has been developed (Figure 6).

Figure 6

The mass spectrum of aldosterone-d4 is shown in Figure 7. The molecular ion of the aldosterone-d4 is much cleaner than aldoste-rone-d7 and consists of 96.9% d4 and 3.1% d3. This indicates the ion selected for monitoring in the LC-MS/MS will be 96.9% as intense as the unlabeled aldosterone molecular ion. This is a vast improvement over the isotopic distribution seen in the aldosterone-d7 internal standard.

Figure 7

Figure 4a and 4b

Mass spectra of aldosterone (top) and aldosterone-d (bottom).

As is typical with steroids of this type, the deuterium labels are in base-sensitive active positions. Exposure of the deuterated aldosterone to basic conditions in solution leads to the exchange of deuterium to the surrounding protic solvent. The result is a reduction in the intensity of the M+8 molecular ion peak. Loss of deuterium can be rapid or slow; the rate of exchange is dependent upon the molecule in question and the pH of the solvent (see Figure 5).

Figure 5


4

The significantly improved mass spec performance of the d4 standard is clearly seen when the molecular ions of aldosterone, aldosterone-d4, and aldosterone-d7 are superimposed (see Figure 8). Two ions are shown for the d7 standard since both d7 and d8 ion could be chosen. Clearly the d4 standard is the internal standard of choice.

Figure 8

3 in 1 Aldosterone Solution Mix

Validation of Deuterium Solution StabilityThe Aldosterone Case Study reinforces the need to validate any deuterated standard for use in an LC-MS/MS clinical assay, with particular attention paid to the following questions:

• Is the deuterated standard stable in the final matrix (Plasma, Buffer, Aqueous Solution, Organic Solution) for the length of time and under the conditions required for use?

• Is the deuterated standard stable in the HPLC mobile phase?

• Has a time course stability validation been carried out?(Stability at t=0 does not mean stability at t=60min or…)

The answers are dependent upon the actual conditions and techniques used. Deuterium containing standards can be used successfully in many instances when validation takes these potential issues into consideration. By analyzing the full range of m/z between analyte and internal standard, an analyst would be able to detect any loss of isotope. However, by relying on just Blank + Internal Standard, the issue would not be detected unless all of the isotope is exchanged giving the appearance of analyte.

The Stable Isotope team at IsoSciences is ready to assist with internal standard selection.

Contact us at: [email protected]

REFERENCES:1. Stefan Grebe and Ravinder J. Singh, Biochem Rev., 32(1), 5-31 (2011)2. Nabil El Tayara et al.,International Journal of Pharmaceutics,19(3), 271 (1984)3. R. Bawejaa, Journal of Liquid Chromatography, 9(12), 2609 (1986)4. F. Masters et al., Analytical Chemistry, 60(19), 2131 (1988)5. Michael Jarvis, AB Sciex, Concord Ontario, Canada, Ultra-Sensitive Analysis of Aldosterone in Serum Using the AB Sciex TripleQuad™ 6500 LC/MS/MS System. www.absciex.com/documents/downloads/literature/6500_aldosterone.pdf


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Deuterated Internal Standards Improved Internal Standards Corresponding Part Number

11-Deoxycorticosterone-d8 11-Deoxycorticosterone-[13C3] 1446711-Deoxycortisol-d2 11-Deoxycortisol-[13C3] 1446411-Deoxycortisol-d5 11-Deoxycortisol-[13C3] 1446417α-Hydroxypregnenolone-d3 17α-Hydroxypregnenolone-[13C2, d2] 1118717α-Hydroxyprogesterone-d8 17α-Hydroxyprogesterone-[13C3] 1033317β-Estradiol-d2 17β-Estradiol-[13C3] 912417β-Estradiol-d3 17β-Estradiol-[13C3] 912417β-Estradiol-d5 17β-Estradiol-[13C3] 912417β-Estradiol-d5 17β-Estradiol-[13C3] 912425-Hydroxyvitamin D2-d3 25-Hydroxyvitamin D2-[13C3] 1003825-Hydroxyvitamin D3-d3 25-Hydroxyvitamin D3-[13C5] 131253-Epi-25-Hydroxyvitamin D3-d3 3-Epi-25-Hydroxyvitamin D3-[13C5] 140415-Hydroxyindoleacetic Acid-d5 5-Hydroxyindoleacetic Acid-[13C6] 15215Aldosterone-d7 Aldosterone-d4 S11214Androstenedione-d7 Androstenedione-[13C3] 9044Biotin-d2 Biotin-d4 15046Cholesterol-d6 Cholesterol-[13C3] 10409Corticosterone-d8 Corticosterone-d4 13035Cortisol-d2 Cortisol-[13C3] S14465Cortisone-d10 Cortisone-[13C3] S14466Cortisone-d2 Cortisone-[13C3] S14466Cortisone-d7 Cortisone-[13C3] S14466Cortisone-d9 Cortisone-[13C3] S14466DHEA-d2 Dehydroepiandrosterone-[13C3] 14317DHEA-d2 Sulfate Dehydroepiandrosterone-d6 Sulfate 9180Dihydrotestosterone-d4 Dihydrotestosterone-[13C3] 6065Estrone-d2 Estrone-[13C3] 9125Estrone-d4 Estrone-[13C3] 9125Folic Acid-d4 Folic Acid-[13C5] 14139Indoxyl Sulfate-d4 Indoxyl Sulfate-[13C6] 14222Nicotinic Acid-d3 (Niacin-d3) Nicotinic Acid-[13C3, 15N] 13257Pregnenolone-d4 Pregnenolone-[13C2, d2] 10402Pregnenolone-d4 Sulfate Pregnenolone-[13C2, d2] Sulfate 10403

Improved Internal StandardsIf currently using a deuterated internal standard listed below, consider switching to an improved internal standard. Contact IsoSciences for promotional pricing.


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Deuterated Internal Standards Improved Internal Standards Corresponding Part Number

Progesterone-d9 Progesterone-[13C3] 10314Pyridoxine-d2 Pyridoxine-d3 P2007098Riboflavin-d6 Riboflavin-[13C4, 15N2] 7072Testosterone-d3 Testosterone-[13C3] 6066Testosterone-d5 Testosterone-[13C3] 6066Thiamine-d3 Thiamine-[13C4] 9209Vitamin B5-[13C, d2] Calcium Pantothenate-[13C,d2]

Vitamin B5-[13C3, 15N] (Calcium Pantothenate-[13C3, 15N])

5065

Vitamin D3-d3 Vitamin D3-[13C3] S12334Vitamin D3-d3 Vitamin D3-[13C5] S13036

Improved Internal StandardsIf currently using a deuterated internal standard listed below, consider switching to an improved internal standard. Contact IsoSciences for promotional pricing.

Page 1 of 3

___________________________________ ______________________________

Peter Greenbacker, IsoSciences LLC Date

Compound: Tetrahydrocortisone-[2H5]

Catalog Number: 14469

Lot Number: SJ4-2014-300A1

Date of Analysis: February 27, 2015

Certificate Expiration: 36 months from Date of Receipt

(Proper Storage and Handling

Required).

Long-Term Storage: The compound should be

stored at ≤ 20 °C, in the dark, in

a tightly sealed container.

Analysis Method Product Specification Product Result

Chemical Purity by HPLC/ELSD ≥ 98%

99.26%

Identity by 1H NMR Conforms to Structure PASS

Identity by Mass Spectrometry Conforms to Structure PASS

Isotope Incorporation by Mass Spectrometry 98 % 2H 99.86% 2H /Molecule

Intended Use

This material is intended only for laboratory use in analytical and R+D applications. It not suitable for human/animal

consumption or for household use.

Hazards

Read Material Safety Data Sheet (MSDS) and understand any potential hazard(s) prior to the use of this product. All

chemicals should be considered potentially hazardous in nature and should only be handled by qualified personnel

using established good laboratory practices.

Certificate of Analysis

Tetrahydrocortisone-[2H5]

O

HOHH2

H2

H2

H2 H2

OHO

OH

Molecular Weight =369.45

Molecular Formula =C21H32O5

Page 2 of 3

Analytical Data 1. HPLC/ELSD

Instrument: Waters Acquity ELSD

Column: Acquity UPLC BEH C18, 2.1 x 75mm, 1.7µm Mobile Phase: A: 0.1% Formic Acid in

Water B: 0.1% Formic Acid in Acetontrile

Gradient: 5% - 95%B over 8 mins., hold 95%B 1 min. Flow Rate: 0.6 mL/min Acquisition Date:

February 27, 2015

2. 1H NMR

Peak #

Ret. Time (min.)

Area (LSU) Height (LSU)

Area % 1 2.48 227.49 8045 0.44 2 2.93 51105.03 1870466 99.26 3 3.04 154.57 8179 0.30

Instrument: Varian Mercury 300 MHz Solvent: Methanol-d4

Page 3 of 3

3. Mass Spectrometry a. Identity

Instrument: Waters Acquity TQD Column:

Acquity UPLC BEH C18 2.1 x 75mm, 1.7µm

Mobile Phase: A: 0.1% Formic Acid in Water

B: 0.1% Formic Acid in Acetontrile

Gradient: 5% - 95%B over 8 mins., hold

95%B for 1 min.

Flow Rate: 0.6 mL/min Ionization: Electrospray positive

Acquisition Date: February 27, 2015

b. Isotope Incorporation Percent

Isotope Enhancement

M+0 0.00%

0.00 M+1

0.00% 0.00

M+2 0.00%

0.00 M+3

0.00% 0.00

M+4 0.70%

0.03 M+5

99.30% 4.97

Total: 100.00%

4.99 % D/Molecule:

99.86 %

Order/Online Catalog: isoSciences.com/catalogTechnical Service: [email protected]/Custom Manufacturing Inquiries: isoSciences.com/request-a-quote

©2016 IsoSciences

Visit IsoSciences.com for additional Stable Isotope product listings.

Product Description Cat. No.Metalaxyl-(phenyl-13C6) 99 atom % 13C 750905

β-N-Methyl-d3-amino-DL-alanine-15N2 98 atom % 15N98 atom % D

759139

Metobromuron-(phenyl-13C6) 99 atom % 13C 777447

4-n-Nonylphenol-2,3,5,6-d4, OD 98 atom % D 747491

4-tert-Octylphenol-(phenyl-13C6) 99 atom % 13C 776416

Oxamyl-1-13C 99 atom % 13C 746266

Penconazol-(propyl-d7) 98 atom % D 774634

Phloretin-(hydroxyphenyl-13C6) 99 atom % 13C 790370

Probucol-propanyl-13C3 99 atom % 13C 705802

Pyrazine-d3-carboxamide-15N 98 atom % 15N98 atom % D

793469

Resoru�n-d6 98 atom % D 705128

Resveratrol-(4-hydroxyphenyl-13C6) 99 atom % 13C 711004

Ricinine-(methyl-d3) 98 atom % D 751073

Spermidine-(butyl-d8) trihydrochloride 98 atom % D 709891

Spermidine-(butyl-13C4) trihydrochloride 99 atom % 13C 740780

Spermine-(butyl-d8) tetrahydrochloride 98 atom % D 705330

Stachydrine-(dimethyl-13C2) monohydrate 99 atom % 13C 755524

cis-Tamoxifen-13C2,15N solution, 1 mg/mL in methanol 99 atom % 13C98 atom % 15N

603252

cis-Tamoxifen-15N-(N,N-dimethyl-13C2) 99 atom % 13C98 atom % 15N

608653

Tamoxifen-(N,N-dimethyl-13C2) 99 atom % 13C 605913

Tamoxifen-(N,N-dimethyl-13C2)-15N 99 atom % 13C99 atom % 15N

608645

Vinblastine-13C2,d3 99 atom % 13C98 atom % D

746274

Yohimbine-(methyl-13C,d3 ester) 99 atom % 13C99 atom % D

731242

Ziprasidone-(piperazine-d8) 97 atom % D 778400

For more information, contact:

Phone: (610) 337-3762 Fax: (610) 337-3782

Email: [email protected]


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Catalog Number Chemical Name Isotope Incorporation10002 1,25-Dihydroxyvitamin D2-[d3] ≥98%S10002 1,25-Dihydroxyvitamin D2-[d3] ≥99%13043 24R,25-Dihydroxyvitamin D3-[26,26,26,27,27,27-d6] ≥98%S13043-0.1 24R,25-Dihydroxyvitamin D3-[26,26,26,27,27,27-d6] ≥98%5154 1,25-Dihydroxyvitamin D3-[d3] ≥97%S5154 1,25-Dihydroxyvitamin D3-[d3] ≥97%S15409-0.1 1,25-Dihydroxyvitamin D3-d6 ≥98%14045 3-Epi-25-hydroxyvitamin D2-[d3] ≥98%S14045 3-Epi-25-hydroxyvitamin D2-[d3] ≥98%14041 3-Epi-25-Hydroxyvitamin D3-[13C5] ≥99%S14041 3-Epi-25-Hydroxyvitamin D3-[13C5] ≥99%11102 3-Epi-25-hydroxyvitamin D3-[d3] ≥98%S11102 3-Epi-25-hydroxyvitamin D3-[d3] ≥98%10038 25-Hydroxyvitamin D2-[25,26,27-13C3] ≥99%S10038 25-Hydroxyvitamin D2-[25,26,27-13C3] ≥99%4176 25-Hydroxyvitamin D2-[d3] ≥97%S4176 25-Hydroxyvitamin D2-[d3] ≥97%S14187-0.1 25-Hydroxyvitamin D2-[d3] Sulfate Sodium Salt ≥98%13085 25-Hydroxyvitamin D3-[26,26,26,27,27,27-d6] Monohydrate ≥98%S13085 25-Hydroxyvitamin D3-[26,26,26,27,27,27-d6] Monohydrate ≥98%4163 25-Hydroxyvitamin D3-[d3] ≥97%S4163 25-Hydroxyvitamin D3-[d3] ≥97%S14188-0.1 25-Hydroxyvitamin D3-[d3] Sulfate Sodium Salt ≥98%S14189-0.1 25-Hydroxyvitamin D3-[d6] Sulfate Sodium Salt ≥98%13125 25-Hydroxyvitamin-D3-[23,24,25,26,27-13C5] ≥99%S13125-0.1 25-Hydroxyvitamin-D3-[23,24,25,26,27-13C5] ≥99%15277 Menaquinone-4-[13C6] (MK4-[13C6]) ≥99%14331 Menaquinone-4-[d7] (MK4-d7) ≥98%16005 Menaquinone-4-[d7] 2,3-Epoxide ≥98%15278 Menaquinone-7-[13C6] (MK7-[13C6]) ≥99%15103 Menaquinone-7-[d7] (MK7-[d7]) ≥98%15279 Menaquinone-9-[13C6] (MK-9-[13C6]) ≥99%15406 Menaquinone-9-[d7] (MK9-[d7]) ≥98%5072 Phytonadione-d7 ≥98%5014 Vitamin D2-[d3] ≥97%

VitaminsVitamins are responsible for a wide range of vital functions. Their identification and quantification in complex matrices are essential to many nutritional studies.


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Catalog Number Chemical Name Isotope IncorporationS5014 Vitamin D2-[d3] ≥97%S14186 Vitamin D2-[d3] Sulfate Sodium Salt ≥98%S13036 Vitamin D3-[23,24,25,26,27-13C5] ≥98%S12334-0.1 Vitamin D3-[25,26,27-13C3] ≥98%S3077 Vitamin D3-[d3] ≥97%S14185 Vitamin D3-[d3] Sulfate Sodium Salt ≥98%S14184 Vitamin D3-[d6] Sulfate Sodium Salt ≥98%S15008 Vitamin D3-d6 ≥98%16003 Vitamin K1-[d7] 2,3-Epoxide ≥98%

Catalog Number Chemical Name Isotope Incorporation9050 L-3,3’-Diiodothyronine-[13C6] ≥99%S9050 L-3,3'-Diiodothyronine-[13C6] ≥99%8204 3-Iodothyronamine-[ethylamino-1,1,2,2-d4] hydrochloride ≥98%8170 Reverse Triiodothyronine-[diiodophenyl-ring-13C6]

hydrochloride≥99%

S8170 Reverse Triiodothyronine-[diiodophenyl-ring-13C6] hydrochloride

≥99%

6022 L-Thyroxine-[L-Tyr-d5] hydrochloride ≥98%S6022 L-Thyroxine-[L-Tyr-d5] hydrochloride ≥98%5031 L-Thyroxine-[L-Tyr-ring-13C6] hydrochloride ≥99%S5031 L-Thyroxine-[L-Tyr-ring-13C6] hydrochloride ≥99%8165 Triiodothyronine-[13C6] hydrochloride ≥99%S8165 Triiodothyronine-[13C6] hydrochloride ≥99%

ThyroxinesIsoSciences has been synthesizing isotopically labeled thyroxines for the past decade. These internal standards continue to be used by diagnostic labs around the world.

VitaminsVitamins are responsible for a wide range of vital functions. Their identification and quantification in complex matrices are essential to many nutritional studies.


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Catalog Number Chemical Name Isotope Incorporation5093 Aldosterone-[2,2,4,6,6,17,21,21-d8] ≥98%S5093 Aldosterone-[2,2,4,6,6,17,21,21-d8] ≥98%S11214 Aldosterone-[d4] ≥98%14315 Allopregnanolone-[d5] ≥98%S14315-0.1 Allopregnanolone-[d5] ≥98%14472 Allotetrahydrocortisol-[D5] ≥98%S14472-0.1 Allotetrahydrocortisol-[D5] ≥98%14473 Allotetrahydrocortisone-[d5] ≥98%S14473-0.1 Allotetrahydrocortisone-[d5] ≥98%15075 Allotetrahydrocortisone-[D4] ≥98%9044 Androst-4-ene-3,17-dione-[13C3] ≥99%S9044 Androst-4-ene-3,17-dione-[13C3] ≥99%14225 5α-Androstane-3α,17β-diol-[d3] ≥98%S14225-0.1 5α-Androstane-3α,17β-diol-[d3] ≥98%S14326-0.1 5α-Androstane-3β,17β-diol-[d3] ≥98%14326 5α-Androstane-3β,17β-diol-[d3] ≥98%S14323-0.1 5α-Androstane-3β,17β-diol-[d4] ≥98%14323 5α-Androstane-3β,17β-diol-[d4] (Dihydroepiandrosterone-d4) ≥98%14324 5α-Androstane-3β,17β-diol-17-Sulfate-[d4] ≥98%S14324-0.1 5α-Androstane-3β,17β-diol-17-Sulfate-[d4] ≥98%14325 5α-Androstane-3β,17β-diol-3-Sulfate-[d4] ≥98%S14325-0.1 5α-Androstane-3β,17β-diol-3-Sulfate-[d4] ≥98%13006 Androstanediol-[d3] Glucuronide Sodium Salt ≥98%S14316-0.1 Androsterone-[d4] ≥98%14235 Androsterone-d4 ≥98%12998 Boldenone-[13C3] ≥98%13101 Chenodeoxycholic Acid-[d4] ≥98%13103 Chenodeoxycholic Acid-[d9] ≥98%9196 Cholesterol-[2,2,3,4,4,6-d6] ≥99%S9196 Cholesterol-[2,2,3,4,4,6-d6] ≥99%10409 Cholesterol-[2,3,4-13C3] ≥99%S10409 Cholesterol-[2,3,4-13C3] ≥99%13098 Cholic Acid-[d4] ≥98%13035 Corticosterone-[9,11,12,12-d4] ≥98%S13035 Corticosterone-[9,11,12,12-d4] ≥98%

SteriodsAs the use of LC-MS/MS continues to expand, so does the IsoSciences ' Steroid product offerings . IsoSciences has the most 13C labeled steroids on the market today.


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Catalog Number Chemical Name Isotope IncorporationS14465 Cortisol-[13C3] ≥99%7193 Cortisol-[d4] ≥98%S7193 Cortisol-[d4] ≥98%15408 Cortisol-[d4]-21-sulfate ≥98%S14466-0.1 Cortisone-[13C3] ≥99%S15407-0.1 Cortisone-[13C3]-21-sulfate ≥98%8056 Cortisone-[d7] ≥98%S8056 Cortisone-[d7] ≥98%S14317-0.1 Dehydroepiandrosterone-[13C3] ≥99%5170 Dehydroepiandrosterone-[d6] ≥97%S5170 Dehydroepiandrosterone-[d6] ≥97%14036 Dehydroepiandrosterone-[d6] Glucuronide ≥98%S14036 Dehydroepiandrosterone-[d6] Glucuronide ≥98%9180 Dehydroepiandrosterone-[d6] sulfate sodium salt ≥97%S9180 Dehydroepiandrosterone-[d6] sulfate sodium salt ≥97%13100 Deoxycholic Acid-[d4] ≥98%13227 Deoxycholic Acid-[d6] ≥98%14467 11-Deoxycorticosterone-[13C3] ≥99%S14467-0.1 11-Deoxycorticosterone-[13C3] ≥99%14464 11-Deoxycortisol-[13C3] ≥99%S14464-0.1 11-Deoxycortisol-[13C3] ≥99%9012 11-Deoxycortisol-[d5] ≥98%S9012 11-Deoxycortisol-[d5] ≥98%15063 21-Desoxycortisol-[d4] ≥98%6065 Dihydrotestosterone-[13C3] ≥99%S6065 Dihydrotestosterone-[13C3] ≥99%15035 Dihydrotestosterone-d4 ≥98%15007 Epiallopregnanolone-d5 ≥98%S15007 Epiallopregnanolone-d5 ≥98%14039 Epiandrosterone-[2,2,4,4-d4] ≥98%S14039 Epiandrosterone-[2,2,4,4-d4] ≥98%8120 Estradiol-[16,16,17-d3] ≥98%9124 17β-Estradiol-[2,3,4-13C3] ≥99%S9124 17β-Estradiol-[2,3,4-13C3] ≥99%14146 17β-Estradiol-13C3 Undecanoate ≥98%



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Catalog Number Chemical Name Isotope Incorporation10157 Estriol-[13C3] ≥99%10311 Estrone, 3-methyl-[13C,d3] ether ≥98%9125 Estrone-[2,3,4-13C3] ≥99%S9125 Estrone-[2,3,4-13C3] ≥99%14319 Etiocholanolone-D5 ≥98%S14319-0.1 Etiocholanolone-D5 ≥98%15094 Exemestane-[13C3] ≥99%13104 Glycochenodeoxycholic Acid-[d4] ≥98%13108 Glycochenodeoxycholic Acid-[d9] ≥98%13443 Glycocholic Acid-[d4] ≥98%13226 Glycodeoxycholic Acid-[d4] ≥98%13229 Glycodeoxycholic Acid-[d6] ≥98%13231 Glycolithocholic Acid-[d4] ≥98%13224 Glycoursodeoxycholic Acid-[ d4] ≥98%12999 4β-Hydroxycholesterol-[2,2,3,4,5-d4] ≥98%12042 4β-Hydroxycholesterol-[d5] ≥98%12997 4β-Hydroxycholesterol-[d7] ≥98%8066 18-Hydroxycorticosterone-[d4] ≥98%S8066 18-Hydroxycorticosterone-[d4] ≥98%13338 18-Hydroxycortisol-[9,11,12,12-d4] ≥98%S13338 18-Hydroxycortisol-[9,11,12,12-d4] ≥98%5101 6β-Hydroxycortisol-[d4] ≥98%14353 16α-Hydroxydehydroepiandrosterone-[d5] ≥98%S14353-0.1 16α-Hydroxydehydroepiandrosterone-[d5] ≥98%14350 7α-Hydroxydehydroepiandrosterone-[d5] ≥98%S14350-0.1 7α-Hydroxydehydroepiandrosterone-[d5] ≥98%14351 7β-Hydroxydehydroepiandrosterone-[D5] ≥98%S14351-0.1 7β-Hydroxydehydroepiandrosterone-[D5] ≥98%S10157 16α-Hydroxyestradiol-[2,3,4-13C3] ≥99%10156 16α-Hydroxyestrone-[2,3,4-13C3] ≥99%S10156 16α-Hydroxyestrone-[2,3,4-13C3] ≥99%11187 17α-Hydroxypregnenolone-[13C2,d2] ≥98%S11187 17α-Hydroxypregnenolone-[13C2,d2] ≥98%10333 17α-Hydroxyprogesterone-[2,3,4-13C3] ≥98%S10333 17α-Hydroxyprogesterone-[2,3,4-13C3] ≥98%



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Catalog Number Chemical Name Isotope Incorporation14479 6β-Hydroxytestosterone-d3 ≥98%S14479 6β-Hydroxytestosterone-d3 ≥98%14352 7-Ketodehydroepiandrosterone-[d5] ≥98%S14352-0.1 7-Ketodehydroepiandrosterone-[d5] ≥98%13099 Lithocholic Acid-[d4] ≥98%6118 2-Methoxy-[13C,d3]-estradiol ≥98%6114 4-Methoxy-[13C,d3]-estradiol ≥98%6117 2-Methoxy-[13C,d3]-estrone ≥98%6113 4-Methoxy-[13C,d3]-estrone ≥98%15061 7-Oxo-Dehydroepiandrosterone-[d5] Sulfate Sodium Salt ≥98%14321 Pregnanetriol-[d5] ≥98%S14321-1.0 Pregnanetriol-[d5] ≥98%14320 Pregnanolone-[d5] ≥98%S14320-0.1 Pregnanolone-[d5] ≥98%15151 Pregnenolone-[2,2,4,4-d4] ≥98%10402 Pregnenolone-[20,21-13C2, 16,16-d2] ≥98%S10402 Pregnenolone-[20,21-13C2, 16,16-d2] ≥98%10403 Pregnenolone-[20,21-13C2, 16,16-d2] sulfate sodium salt ≥98%S10403-0.1 Pregnenolone-[20,21-13C2, 16,16-d2] sulfate sodium salt ≥98%10314 Progesterone-[2,3,4-13C3] ≥99%S10314 Progesterone-[2,3,4-13C3] ≥99%14441 Progesterone-[D9] ≥98%13105 Taurochenodeoxycholic Acid-[d4] Na Salt ≥98%13107 Taurochenodeoxycholic Acid-[d9] Na Salt ≥98%13232 Taurocholic Acid-[d4] Na Salt ≥98%13228 Taurodeoxycholic Acid-[d6] Sodium Salt ≥98%13225 Taurodeoxycycholic Acid-[d4] Sodium Salt Hydrate ≥98%13230 Taurolithocholic Acid-[d4] Sodium Salt ≥98%13106 Tauroursodeoxycholic Acid-[d4] Na Salt ≥98%6066 Testosterone-[13C3] ≥99%S6066 Testosterone-[13C3] ≥99%14038 Testosterone-[16,16,17-d3] Glucuronide ≥98%S14038 Testosterone-[16,16,17-d3] Glucuronide ≥98%14037 Testosterone-[d3] ≥98%S14037 Testosterone-[d3] ≥98%



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Catalog Number Chemical Name Isotope IncorporationS14322-1.0 Testosterone-[d3] Cypionate ≥98%S14018-1.0 Testosterone-[d3] Decanoate ≥98%S14005-1.0 Testosterone-[d3] Heptanoate ≥98%S14006-1.0 Testosterone-[d3] Isocaproate ≥98%S14007-1.0 Testosterone-[d3] Phenylpropionate ≥98%S14008-1.0 Testosterone-[d3] Propionate ≥98%S14009-1.0 Testosterone-[d3] Undecanoate ≥98%3009 Testosterone-[d5] ≥98%S3009 Testosterone-[d5] ≥98%15272 Tetrahydro-11-deoxycortisol-[d5] ≥98%12182 3α,5β-Tetrahydroaldosterone-[d6] ≥98%S12182 3α,5β-Tetrahydroaldosterone-[d6] ≥98%14999 Tetrahydrocorticosterone-[d4] ≥98%S14999 Tetrahydrocorticosterone-[d4] ≥98%14468 Tetrahydrocortisol-[d5] ≥98%



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Catalog Number Chemical Name Isotope Incorporation11036 Abrine-[d3] ≥98%7145-AAMU 5-Acetylamino-6-amino-3-methyluracil-[13C4,15N3] ≥98%13260 N-Acetyl-N-deisopropyl-Zilpaterol-[d3] ≥98%S14414 Adipic Acid-[D4] ≥98%S14406-1.0 L-Alanine-[13C3] ≥98%10169 Aldicarb sulfone-[13C2,d3] ≥98%10168 Aldicarb sulfoxide-[13C2,d3] ≥98%10122 Aldicarb-[13C2,d3] ≥98%15159 alpha-Ionone-[13C3] ≥98%S12038-1.0 2-Amino-6-methylmercaptopurine-[13C, d3] ≥98%15264 β-Aminomethyl-L-alanine-[13C, 15N2] Dihydrochloride ≥99%5109 p-Anisic Acid-[13C6] ≥99%13415 Arachidonic acid-[16,16,17,17,18,18,19,19,20,20,20-d11] ≥98%9039 Arachidonic acid-[5,6,8,9,11,12,14,15-d8] ≥98%S14407 L-Arginine-[13C6] Hydrochloride ≥98%S14493-1.0 Asparagine-[13C4] Hydrate ≥99%15217 Atrazine-[13C3,15N3] ≥98%B2007072 Barbituric Acid-[13C4,15N2] ≥98%13005 Bentazone-[13C10,15N] ≥98%8089CD 1-Benzyl-4-methylenepiperidine-[13C,d6] ≥98%15160 beta-Ionone-[13C3] ≥98%15127 tert-Butyl 4-aminobenzoate-[13C6] ≥98%8144 (+/-)-Catechin-[13C3] ≥99%15310 (+/-)-Catechin-[13C3] Gallate ≥99%S15017-0.1 Catechol-[d4] ≥98%13420 Chlophedianol-[13C6] ≥99%11162 4-Chloro-2-Methylphenoxyacetic Acid-[13C8] ≥99%S15242-1.0 Choline-[13C2] Chloride ≥98%15341 Choline-[13C3] Chloride ≥95%S14416-1.0 L-Citrulline-[D7] ≥98%15218 Clodinafop-propargyl-[13C6] ≥98%9116 m-Coumaric acid-[13C3] ≥99%9115 p-Coumaric acid-[13C3] ≥99%12303 p-Cresol Sulfate-[ d7] Potassium Salt ≥98%11252 o-Cresol-[13C6] ≥99%

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Catalog Number Chemical Name Isotope Incorporation14194 Cytosine-13C2, 15N3 ≥98%S14411-1.0 Decanoyl-L-Carnitine-[d3] Hydrochloride ≥98%5060 Desethylamodiaquine-[d5] ≥97%15205 1,5-Diaminonaphthalene-[15N2] ≥98%D2006054 Dicamba-[13C6] ≥99%6054 3,6-Dichloro-2-hydroxybenzoic-[13C6] Acid ≥99%S15243-1.0 1,3-Dilinoleoyl glycerol-[13C3] ≥98%S14372-1.0 1,3-Dilinoleoyl-rac-glycerol-[d5] ≥98%13053 Docosahexaenoic Acid ethyl ester-[D5] ≥98%9036 cis-4,7,10,13,16,19-Docosahexaenoic Acid-[21,21,22,22,22-d5] ≥98%13175 cis-4,7,10,13,16,19-Docosahexaenoic Acid-[21,21,22,22,22-d5]

Methyl Ester ≥98%

S14412-1.0 Dodecanoyl-L-carnitine-[d3] Hydrochloride ≥98%S10399 Dopamine-[d4] Hydrochloride ≥98%15365 Doxycycline-[d3] Hydrochloride ≥98%15366 Doxycycline-d5 ≥95%13218 Efavirenz-[13C6] ≥99%13003 Eicosapentaenoic Acid ethyl ester-[D5] ≥98%9037 cis-5,8,11,14,17-cis-5,8,11,14,17-Eicosapentaenoic

acid-[19,19,20,20,20-d5]≥98%

13180 cis-5,8,11,14,17-Eicosapentaenoic acid-[19,19,20,20,20-d5] Methyl Ester

≥98%

8151 (+/-)-Epicatechin -[13C3] ≥99%S10400-0.1 Epinephrinee-D6 ≥98%15221 Erucic Acid-[d18] ≥98%15185 Ethyl Maltol-[d5] ≥90%15396 Etiracetam-[d3] (Racemate) ≥99%15158 Eucalyptol-[13C d3] ≥98%14001 Everolimus-[d4] ≥98%S14001 Everolimus-[d4] ≥98%13421 Fenamidone-[13C6] ≥99%9114 Ferulic acid-[13C3] ≥99%12344 FMOC-L-Glutamic Acid-[13C5,15N]-5-t-butyl ester ≥98%14344 Gabapentin-13C3 ≥98%13416 Galangin-[13C3] ≥99%



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Catalog Number Chemical Name Isotope Incorporation15314 (+/-)-Gallocatechin-[13C3] ≥99%15308 (+/-)-Gallocatechin-[13C3] Gallate ≥99%S15241 gamma-Butyrolactone-[13C2] ≥98%S14373-1.0 gamma-Butyrolactone-[D6] ≥98%S14374-1.0 Glucose-[13C6] ≥98%S14494-1.0 Glycylglycine-[13C4] ≥99%S14415-1.0 Hexadecanoic Acid-[D4] ≥98%S15239 Hexanedioic Acid-[d8] ≥98%9117 Hippuric Acid-[13C6] ≥99%S14130 DL-Homocysteine-d4 ≥98%S10411-0.1 (+-)-4-Hydroxy-3-methoxymandelic Acid-D3 ≥98%S10413-0.1 4-Hydroxy-3-Methoxyphenyl-[d3]-acetic-[d2] Acid (HVA-[d5]) ≥98%S15240-1.0 2-Hydroxybutyrate-[d3] Sodium Salt ≥98%11222 5-Hydroxyindole-[d5] ≥98%S10412 5-Hydroxyindole-4,6,7-D3-3-acetic-D2 Acid ≥98%15215 5-Hydroxyindoleacetic acid-[13C6] ≥98%S14371-1.0 5-Hydroxytryptophan-[d3] ≥98%S12354 5-Hydroxytyramine-D4 ≥98%12058 Indole-[d6] ≥98%14222 Indoxyl Sulfate-[13C6] Potassium Salt ≥99%7158 Iopromide-[d3] ≥98%S14408-1.0 L-Isoleucine-[13C6] ≥98%15263 Isophorone Diamine-[13C,15N2] ≥98%10230 Isophorone-[2,4,4,6,6-d5] ≥97%13418 Kaempferol-[13C3] ≥99%15244 Leucine-[13C6] ≥98%S14495-1.0 Linoleic Acid-13C18 ≥99%10092 (+/-)-Mecamylamine-[13C4,15N] Hydrochloride ≥98%10363 Metalaxyl-[13C6] ≥99%S11236 (+/-)-Metanephrine-a,B,B-[d3] ≥98%S14409-1.0 L-Methionine-[13C5] ≥98%3130 3-Methoxy-[13C,d3]-benzaldehyde ≥98%S10417-1.0 3-Methoxytyramine-[d4] Hydrochloride (3MT-[d4]) ≥98%15161 Methyl Anthranilate-[13C6] ≥99%13018 Methyl-d3 Malonic Acid ≥98%



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Catalog Number Chemical Name Isotope Incorporation15219 4,4'-Methylenedianiline-[15N2, 13C] ≥98%12281 6-Methylmercaptopurine-[13C,d3] ≥98%S12281-1.0 6-Methylmercaptopurine-[13C,d3] ≥98%12174 6-Methylthioguanine-[13C,d3] ≥98%7145-X003 3-Methylxanthine-[13C4,15N3] ≥98%13419 Myricetin-[13C3] ≥99%S10401-0.1 Norepinephrine-[d6] Hydrochloride ≥98%S11237 (+/-)-Normetanephrine-α,β,β-[d3] Hydrochloride ≥98%S14375-1.0 Oleic Acid-[13C5] ≥99%S14390-0.1 2-Oxovaleric Acid-[d7] ≥98%8112 Paclitaxel-[d5] ≥98%S14410-1.0 Palmitoyl-L-Carnitine-[d3] Hydrochloride ≥98%15181 Piperonal-[13C,D2] ≥95%4032 Probucol-[13C3] ≥99%9270 Pyrimethanil-[13C,15N2] ≥98%13417 Quercetin-[13C3] ≥99%10286 Rapamycin-[d3] ≥98%6166 Resorufin-[d6] ≥98%9054 Resveratrol-[13C6] ≥99%11035 Ricinine-[d3] ≥98%S11109 Saxitoxin-[15N4] Bis-heptafluorobutyric acid salt ≥98%10326 Spermidine-[13C4].3HCl ≥99%9043 Spermidine-[d8].3HCl ≥98%7095 Spermine-[d8].4HCl ≥98%S14404-1.0 L-Taurine-[13C2] ≥98%S14405-1.0 Taurine-[d4] ≥98%13349 Tonabersat-d6 ≥98%3201 Triazole-[13C2,15N3] ≥98%15206 Trimethylamine-N-oxide-[13C3] ≥98%15163 2,3,5-Trimethylpyrazine-[d9] ≥98%7057 cis-Urocanic Acid-[13C3] ≥99%10075 Yohimbine-[13C,d3] ≥99%



18

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Product Description Cat. No.Metalaxyl-(phenyl-13C6) 99 atom % 13C 750905

β-N-Methyl-d3-amino-DL-alanine-15N2 98 atom % 15N98 atom % D

759139

Metobromuron-(phenyl-13C6) 99 atom % 13C 777447

4-n-Nonylphenol-2,3,5,6-d4, OD 98 atom % D 747491

4-tert-Octylphenol-(phenyl-13C6) 99 atom % 13C 776416

Oxamyl-1-13C 99 atom % 13C 746266

Penconazol-(propyl-d7) 98 atom % D 774634

Phloretin-(hydroxyphenyl-13C6) 99 atom % 13C 790370

Probucol-propanyl-13C3 99 atom % 13C 705802

Pyrazine-d3-carboxamide-15N 98 atom % 15N98 atom % D

793469

Resoru�n-d6 98 atom % D 705128

Resveratrol-(4-hydroxyphenyl-13C6) 99 atom % 13C 711004

Ricinine-(methyl-d3) 98 atom % D 751073

Spermidine-(butyl-d8) trihydrochloride 98 atom % D 709891

Spermidine-(butyl-13C4) trihydrochloride 99 atom % 13C 740780

Spermine-(butyl-d8) tetrahydrochloride 98 atom % D 705330

Stachydrine-(dimethyl-13C2) monohydrate 99 atom % 13C 755524

cis-Tamoxifen-13C2,15N solution, 1 mg/mL in methanol 99 atom % 13C98 atom % 15N

603252

cis-Tamoxifen-15N-(N,N-dimethyl-13C2) 99 atom % 13C98 atom % 15N

608653

Tamoxifen-(N,N-dimethyl-13C2) 99 atom % 13C 605913

Tamoxifen-(N,N-dimethyl-13C2)-15N 99 atom % 13C99 atom % 15N

608645

Vinblastine-13C2,d3 99 atom % 13C98 atom % D

746274

Yohimbine-(methyl-13C,d3 ester) 99 atom % 13C99 atom % D

731242

Ziprasidone-(piperazine-d8) 97 atom % D 778400

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